CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of the following U.S. Provisional Applications having serial numbers: 63/074,433, filed September 3, 2020; 63/084,433, filed September 28, 2020; 63/088,335, filed October 6, 2020; 63/110,705, filed November 6, 2020 and 63/112,320, filed on November 11, 2020, the entire contents of each are incorporated herein by reference.

BACKGROUND

[1] Inflammation can be a protective response to harmful stimuli, such as invading pathogens, damaged cells, toxic compounds, or cancerous cells. However excessive inflammatory responses, or inflammatory responses that fail to resolve, can result in serious adverse effects, including tissue damage and even death.

[2] Thus, there is a need for new compositions and methods for resolving inflammation.

SUMMARY

[3] Provided herein are methods and compositions related to the use of anti-inflammatory bacteria for the resolution of an inflammatory response (e.g., resolution of an ongoing inflammatory response) in a subject. In some embodiments, the methods and compositions provided herein resolve an inflammatory response, e.g., as described herein. Bacteria are anti-inflammatory, e.g., if the bacteria reduce (e.g., significantly reduce) the levels of a pro- inflammatory cytokine such as IL-8, IL-6, IL-ip, and/or TNFa, e.g., in an assay described herein. An inflammatory response is resolved, e.g., if the levels of a pro-inflammatory cytokine such as IL-8, IL-6, IL-ip, and/or TNFa are reduced (e.g., significantly reduced), e.g., in an assay described herein. In some embodiments, the methods and compositions provided herein are for the reduction of inflammatory cytokine expression (e.g., IL-8, IL-6, IL-ip, and/or TNFa expression). In some embodiments, the methods and compositions provided herein are for the reduction of IL-8, IL-6, and/or TNFa expression. In some embodiments, the methods and compositions provided herein are for the reduction of IL-6, IL-8 and/or TNFa production from myeloid cells (e.g., in an assay described herein). In some embodiments, the methods and compositions provided herein are for the reduction of IL-6, IL-8 and/or TNFa production from myeloid cells but not from T-cells (e.g., in an assay described herein).

[4] In some embodiments, the methods and compositions provided herein do not reduce (e.g., do not significantly reduce or suppress) the Type I interferon response, e.g., do not reduce (e.g., do not significantly reduce or suppress) IFNa and/or IFNp levels, e.g., as determined in an assay described herein. In some embodiments, the methods and compositions provided herein do not reduce (e.g., do not significantly reduce or suppress) IFNa and/or IFNp levels, e.g., as determined in an assay described herein.

[5] In some embodiments, the methods and compositions provided herein resolve an inflammatory response (e.g., an ongoing inflammatory response) and do not reduce (e.g., do not significantly reduce or suppress) the Type I interferon response, e.g., do not reduce (e.g., do not significantly reduce or suppress) IFNa and/or IFNp levels.

[6] In some embodiments, the methods and compositions provided herein do not alter (e.g., do not significantly alter) the anti-viral TLR3-mediated Type 1 interferon (alpha and beta) response, e.g., as determined in an assay described herein.

[7] In some embodiments, the methods and compositions provided herein resolve an inflammatory response (e.g., an ongoing inflammatory response) and do not alter (e.g., do not significantly alter) the anti-viral TLR3 -mediated Type 1 interferon (alpha and beta) response.

[8] In some embodiments, the methods and compositions provided herein do not alter (e.g., do not significantly alter) interferon-gamma (IFNy) production by immune cells, e.g., as determined in an assay described herein.

[9] In some embodiments, the methods and compositions provided herein resolve an inflammatory response (e.g., an ongoing inflammatory response) and do not alter (e.g., do not significantly alter) interferon-gamma (IFNy) production by immune cells.

[10] In some embodiments, the methods and compositions provided herein do not alter (e.g., do not significantly alter) an immune cell subset (e.g., as determined by absolute number and/or percentage), wherein the immune cell subset is CD8 T lymphocytes, B lymphocytes, and/or myeloid lineage cells, e.g., as determined in an assay described herein.

[11] In some embodiments, the methods and compositions provided herein resolve an inflammatory response (e.g., an ongoing inflammatory response) and do not alter (e.g., do not significantly alter) an immune cell subset (e.g., as determined by absolute number and/or percentage), wherein the immune cell subset is CD8 T lymphocytes, B lymphocytes, and/or myeloid lineage cells.

[12] In some embodiments, the methods and compositions provided herein do not reduce (e.g., do not significantly reduce) an antigen-specific antibody response, e.g., as determined in an assay described herein.

[13] In some embodiments, the methods and compositions provided herein resolve an inflammatory response (e.g., an ongoing inflammatory response) and do not reduce (e.g., do not significantly reduce) an antigen-specific antibody response.

[14] In certain embodiments, the anti-inflammatory bacteria are a Prevotella histicola strain. In certain embodiments, the anti-inflammatory bacteria are a. Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella histicola strain is Prevotella histicola Strain B (NRRL accession number B 50329).

[15] In some embodiments, the anti-inflammatory bacteria such as the Prevotella histicola strain are administered in a pharmaceutical composition and/or a solid dosage form (e.g., tablet or capsule).

[16] In some embodiments, the pharmaceutical compositions comprising antiinflammatory bacteria are prepared as solid dosage forms (e.g., such as tablets or capsules). In some embodiments, the pharmaceutical compositions comprise about 3 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the anti-inflammatory bacteria. In some embodiments, the pharmaceutical compositions comprise about 8 x 10 ¹⁰ to about 1.3 x 10 ¹² total cells of the anti-inflammatory bacteria. In some embodiments, the pharmaceutical compositions comprise about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the anti-inflammatory bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a capsule e.g., an enteric coated capsule.

[17] In some embodiments, the anti-inflammatory bacteria are a. Prevotella histicola strain. In some embodiments, the Prevotella histicola strain is Prevotella histicola Strain B (NRRL accession number B 50329). In certain embodiments of the methods provided herein, at least 4 x 10 ¹⁰ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, at least 4 x 10 ¹⁰ cells, 5 x 10 ¹⁰ cells, 6 x 10 ¹⁰ cells, 7 x 10 ¹⁰ cells, 8 x 10 ¹⁰ cells, 9 x 10 ¹⁰ cells, 1.0 x 10 ¹¹ cells, 1.1 x 10 ¹¹ cells, 1.2 x 10 ¹¹ cells, 1.3 x 10 ¹¹ cells, 1.4 x IO ¹¹ cells, 1.5 x IO ¹¹ cells, 1.6 x IO ¹¹ cells, 1.7 x IO ¹¹ cells, 1.8 x IO ¹¹ cells, 1.9 x IO ¹¹ cells, 2.0 x IO ¹¹ cells, 2.1 x IO ¹¹ cells, 2.2 x IO ¹¹ cells, 2.3 x IO ¹¹ cells, 2.4 x IO ¹¹ cells, 2.5 x IO ¹¹ cells, 2.6 x IO ¹¹ cells, 2.7 x IO ¹¹ cells, 2.8 x IO ¹¹ cells, 2.9 x IO ¹¹ cells, 3.0 x IO ¹¹ cells, 3.1 x IO ¹¹ cells, 3.2 x IO ¹¹ cells, 3.3 x IO ¹¹ cells, 3.4 x IO ¹¹ cells, 3.5 x IO ¹¹ cells,

3.6 x IO ¹¹ cells, 3.7 x IO ¹¹ cells, 3.8 x IO ¹¹ cells, 3.9 x IO ¹¹ cells, 4.0 x IO ¹¹ cells, 4.1 x IO ¹¹ cells, 4.2 x IO ¹¹ cells, 4.3 x IO ¹¹ cells, 4.4 x IO ¹¹ cells, 4.5 x IO ¹¹ cells, 4.6 x IO ¹¹ cells, 4.7 x IO ¹¹ cells, 4.8 x IO ¹¹ cells, 4.9 x IO ¹¹ cells, 5.0 x IO ¹¹ cells, 5.1 x IO ¹¹ cells, 5.2 x IO ¹¹ cells, 5.3 x IO ¹¹ cells, 5.4 x IO ¹¹ cells, 5.5 x IO ¹¹ cells, 5.6 x IO ¹¹ cells, 5.7 x IO ¹¹ cells, 5.8 x IO ¹¹ cells, 5.9 x IO ¹¹ cells, 6.0 x IO ¹¹ cells, 6.1 x IO ¹¹ cells, 6.2 x IO ¹¹ cells, 6.3 x IO ¹¹ cells, 6.4 x IO ¹¹ cells, 6.5 x IO ¹¹ cells, 6.6 x IO ¹¹ cells, 6.7 x IO ¹¹ cells, 6.8 x IO ¹¹ cells, 6.9 x IO ¹¹ cells, 7.0 x IO ¹¹ cells, 7.1 x IO ¹¹ cells, 7.2 x IO ¹¹ cells, 7.3 x IO ¹¹ cells, 7.4 x IO ¹¹ cells, 7.5 x IO ¹¹ cells, 7.6 x IO ¹¹ cells, 7.7 x IO ¹¹ cells, 7.8 x IO ¹¹ cells, 7.9 x IO ¹¹ cells, or 8.0 x IO ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, from 4 x IO ¹⁰ cells to 1.6 x 10 ¹² cells of the Prevotella histicola strain are administered to the subject daily. In certain embodiments, from 4 x IO ¹⁰ cells to 8 x IO ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In certain embodiments, from 8 x IO ¹⁰ cells to 8 x IO ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In certain embodiments, from 1.6 x IO ¹¹ cells to 8 x IO ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, about 8 x IO ¹⁰ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, about

1.6 x IO ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, about 3.2 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, about 8 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily. In some embodiments, about 1.6 x 10 ¹¹ cells of Prevotella histicola strain are administered to the subject once daily. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment).

[18] In certain embodiments, provided herein are solid dosage forms comprising the Prevotella histicola bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, each tablet comprises about 3.2 x 10 ¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, the solid dosage form is a capsule e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x IO ¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 1.6 x 10 ¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 3.2 x 10 ¹¹ total cells (e.g., 3.35 x 10 ¹¹ total cells) of the Prevotella histicola bacteria.

[19] In certain embodiments, from 1.6 x IO ¹⁰ cells to 16 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.

In certain embodiments, from 8 x 10 ¹¹ cells to 16 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In certain embodiments, from 8 x IO ¹⁰ cells to 8 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In certain embodiments, from 8 x IO ¹⁰ cells to 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In certain embodiments, from 1.6 x 10 ¹¹ cells to 8 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 8 x 10 ¹⁰ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 3.2 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 6.4 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 8 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject once daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then about 1.6 x 10 ¹¹ cells of the Prevotella histicola strain are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment), e.g., in a solid dosage form.

[20] In some embodiments, about 9.6 x 10 ¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily. [21] In some embodiments, about 12.8 x 10 ¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[22] In some embodiments, about 16 x 10 ¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[23] In some embodiments, about 9.6 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[24] In some embodiments, about 9.6 x 10 ¹¹ to about 12.8 x 10 ¹¹ total cells of the Prevotella histicola strain are administered to the subject daily.

[25] In some embodiments, about 12.8 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[26] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[27] In some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[28] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[29] In some embodiments, the pharmaceutical composition comprises about 3.2 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[30] In some embodiments, the pharmaceutical composition comprises about 6.4 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[31] In some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[32] In some embodiments, the anti-inflammatory bacteria such as the Prevotella histicola strain are administered in a pharmaceutical composition (e.g., a pharmaceutical composition provided herein). In certain embodiments, the pharmaceutical composition is a solid dose form provided herein. In some embodiments, the pharmaceutical composition comprises a blend of freeze-dried powder of the anti-inflammatory bacteria such as the Prevotella histicola and excipients (e.g., an encapsulated freeze-dried powder of the antiinflammatory bacteria such as a. Prevotella histicola strain provided herein and excipients). In some embodiments, the pharmaceutical composition comprises freeze-dried (e.g., lyophilized) powder of anti-inflammatory bacteria in a capsule. In some embodiments, the capsule comprises gelatin or HPMC. In some embodiments, the capsule is enteric coated. In some embodiments, the pharmaceutical composition comprises a formulation of Prevotella histicola Strain B comprising freeze-dried powder of Prevotella histicola and excipients. In some embodiments, the excipients include mannitol, magnesium stearate and colloidal silicon dioxide. In some embodiments, each capsule contains about 8.0 x IO ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to a subject once daily. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of ^.Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to a subject twice daily. In some embodiments, 2 powder-containing capsules are administered to the subject daily. In some embodiments, 1 powder-containing capsule is administered to the subject daily. In some embodiments, each powder-containing capsule contains about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of ^.Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 4 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject once daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of ^.Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject twice daily. In some embodiments, 2 powdercontaining enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 ¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment). In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 8.0 x IO ¹⁰ cells of a. Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) is administered to the subject daily.

[33] In some embodiments, the pharmaceutical composition is formulated as multiple enteric-coated mini-tablets of the anti-inflammatory bacteria such as Prevotella histicola drug product fdled into capsules. In some embodiments, the pharmaceutical composition is formulated as multiple enteric-coated mini-tablets of the anti-inflammatory bacteria such as Prevotella histicola drug product fdled into capsules (mini-tablets in capsules (MICs)). In some embodiments, the capsule comprises gelatin or HPMC. In some embodiments, the pharmaceutical composition comprises excipients (e.g., pharmaceutically acceptable excipients). In some embodiments, the pharmaceutical composition comprises mannitol, colloidal silicon dioxide, hydroxypropyl cellulose, crospovidone, and magnesium stearate. In some embodiments, each capsule contains about 8.0 x IO ¹⁰ cells of ^.Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered to a subject daily. In some embodiments, 2 capsules are administered to the subject daily. In some embodiments, 1 capsule is administered to the subject daily. In some embodiments, each MIC contains about 8.0 x 10 ¹⁰ cells of a. Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 MICs are administered to a subject daily. In some embodiments, 2 MICs are administered to the subject daily. In some embodiments, 1 MIC is administered to the subject daily.

[34] In some embodiments, the Prevotella histicola strain is a strain comprising at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella histicola strain is the Prevotella histicola Strain B (NRRL accession number B 50329).

[35] In some aspects, the disclosure provides use of the anti-inflammatory bacteria such as a Prevotella histicola strain provided herein and/or a pharmaceutical composition (e.g., a pharmaceutical composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for the preparation of a medicament for the performance of a therapeutic method provided herein. In some aspects, the disclosure provides the antiinflammatory bacteria such as a Prevotella histicola strain provided herein and/or a pharmaceutical composition (e.g, a pharmaceutical composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for use in the performance of a therapeutic method provided herein.

[36] In certain embodiments, the anti-inflammatory bacteria are a Veillonella parvulci strain. In certain embodiments, the anti-inflammatory bacteria are a Veillonella parvula strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Veillonella parvula strain A (ATCC Deposit Number PTA- 125691). In some embodiments, the Veillonella parvula strain is Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[37] In some embodiments, the anti-inflammatory bacteria such as the Veillonella parvula strain are administered in a pharmaceutical composition and/or a solid dosage form.

[38] In some embodiments, the anti-inflammatory bacteria are a Veillonella parvula strain. In some embodiments, the Veillonella parvula strain is Veillonella parvula strain A (ATCC Deposit Number PTA- 125691). In some embodiments, the bacterial composition comprises at least about 3 x 10 ¹⁰ total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[39] In some embodiments, the bacterial composition comprises about 3 x 10 ¹⁰ total cells of Veillonella parvula, e.g. , of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[40] In some embodiments, the bacterial composition comprises about 4.5 x 10 ¹⁰ total cells of Veillonella parvula, e.g. , of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[41] In some embodiments, the bacterial composition comprises about 1.5 x 10 ⁿ total cells of Veillonella parvula, e.g. , of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[42] In some embodiments, the bacterial composition comprises about 7.5 x 10 ¹¹ total cells of Veillonella parvula, e.g. , of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[43] In some embodiments, the bacterial composition comprises about 1.5 x 10 ¹² total cells of Veillonella parvula, e.g. , of Veillonella parvula strain A (ATCC Deposit Number PTA- 125691). [44] In some embodiments, the bacterial composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of Veillonella parvula, e.g., of Veillonella parvulci strain A (ATCC Deposit Number PTA-125691).

[45] In some embodiments, the bacterial composition comprises about 4.5 x 10 ¹⁰ to about

1.5 x 10 ¹² total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[46] In some embodiments, the bacterial composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹¹ total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[47] In some embodiments, the bacterial composition comprises about 4.5 x 10 ¹⁰ to about

1.5 x 10 ¹¹ total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[48] In some embodiments, the bacterial composition comprises about 1.5 x 10 ⁿ to about

1.5 x 10 ¹² total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[49] In some embodiments, the bacterial composition comprises about 1.5 x 10 ⁿ to about

7.5 x 10 ¹¹ total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[50] In some embodiments, the bacterial composition comprises about 7.5 x 10 ⁿ to about

1.5 x 10 ¹² total cells of Veillonella parvula, e.g., of Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[51] In certain embodiments, the pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1 x 10 ¹⁰ total cells, about 2 x 10 ¹⁰ total cells, about 3 x 10 ¹⁰ total cells, about 4 x 10 ¹⁰ total cells, about 4.5 x 10 ¹⁰ total cells, about 5 x 10 ¹⁰ total cells, about 6 x 10 ¹⁰ total cells, about 7 x 10 ¹⁰ total cells, about 8 x 10 ¹⁰ total cells, about 9 x 10 ¹⁰ total cells, about 1 x 10 ¹¹ total cells, about 1.5 x 10 ¹¹ total cells, about 2 x 10 ¹¹ total cells, about 3 x 10 ¹¹ total cells, about 4 x 10 ¹¹ total cells, about 5 x 10 ¹¹ total cells, about 6 x 10 ¹¹ total cells, about 7 x 10 ¹¹ total cells, about 7.5 x 10 ¹¹ total cells, about 8 x 10 ¹¹ total cells, about 9 x 10 ¹¹ total cells, about 1 x 10 ¹² total cells, about 1.5 x 10 ¹² total cells, about 2 x 10 ¹² total cells of the Veillonella parvula bacteria.

[52] In certain embodiments, the pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises at least 1 x 10 ¹⁰ total cells (e.g., at least 1 x 10 ¹⁰ total cells, at least 2 x 10 ¹⁰ total cells, at least 3 x 10 ¹⁰ total cells, at least 4 x 10 ¹⁰ total cells, at least 4.5 x 10 ¹⁰ total cells, at least 5 x 10 ¹⁰ total cells, at least 6 x 10 ¹⁰ total cells, at least 7 x IO ¹⁰ total cells, at least 8 x IO ¹⁰ total cells, at least 9 x IO ¹⁰ total cells, at least 1 x 10 ¹¹ total cells, at least 1.5 x 10 ¹¹ total cells, at least 2 x 10 ¹¹ total cells, at least 3 x

10 ¹¹ total cells, at least 4 x 10 ¹¹ total cells, at least 5 x 10 ¹¹ total cells, at least 6 x 10 ¹¹ total cells, at least 7 x 10 ¹¹ total cells, at least 7.5 x 10 ¹¹ total cells, at least 8 x 10 ¹¹ total cells, at least 9 x 10 ¹¹ total cells, at least 1 x 10 ¹² total cells, at least 1.5 x 10 ¹² total cells, at least 2 x

10 ¹² total cells of the Veillonella parvulci bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 7.5 x 10 ¹¹ total cells the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ¹² total cells the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ⁿ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ⁿ to about 7.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 7.5 x 10 ¹¹ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria.

[53] In certain embodiments, provided herein are solid dosage forms comprising the Veillonella parvula bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 3 x IO ¹⁰ total cells of the Veillonella parvula bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 3 x IO ¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 3 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 3 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 3 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, each capsule comprises about 4.5 x IO ¹⁰ total cells of the Veillonella parvulci bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 4.5 x IO ¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 4.5 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 4.5 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 4.5 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.5 x 10 ¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.5 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.5 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.5 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, the Veillonella parvula bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Veillonella parvula bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the Veillonella parvula bacteria are gamma irradiated.

[54] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the capsule comprises about 3 x 10 ¹⁰ total cells of the Veillonella parvula bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 4.5 x 10 ¹⁰ total cells of the Veillonella parvula bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the Veillonella parvula bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Veillonella parvula bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the Veillonella parvula bacteria are gamma irradiated. [55] In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 18mm in diameter. In some embodiments, the tablet comprises about 3 x 10 ¹⁰ total cells of the Veillonella parvula bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 4.5 x IO ¹⁰ total cells of the Veillonella parvula bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the Veillonella parvula bacteria in the tablet are lyophilized. In some embodiments, the Veillonella parvula bacteria of the tablet are gamma irradiated.

[56] In some embodiments, the solid dosage form comprises a mini-tablet. In some embodiments, the mini-tablet is enteric coated. In some embodiments, the mini-tablet is from 1mm to 4mm in diameter. In some embodiments, the mini-tablet (e.g., enteric coated minitablet) is a 1mm mini-tablet, 1.5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet. In some embodiments, the solid dosage form comprises mini-tablets that comprise about 3 x IO ¹⁰ total cells of the Veillonella parvula bacteria (e.g., total dose of a plurality of mini -tablets). In some embodiments, the solid dosage form comprises minitablets that comprise about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria (e.g., total dose of a plurality of mini -tablets). In some embodiments, the Veillonella parvula bacteria in the mini-tablets are lyophilized. In some embodiments, the Veillonella parvula bacteria in the mini-tablet are gamma irradiated.

[57] In some embodiments, the mini -tablets (e.g., enteric coated mini-tablets) are contained in a capsule. In some embodiments, the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule comprises a non-enteric coating (e.g., gelatin) (e.g., is coated with a non-enteric coating). In some embodiments, the capsule comprises a non-enteric coating. In some embodiments, the capsule comprises gelatin or HPMC. In some embodiments, the capsule comprises gelatin or HPMC. In some embodiments, the mini-tablets (e.g., enteric coated mini -tablets) that comprise about 3 x 10 ¹⁰ total cells of the Veillonella parvula bacteria are contained in a capsule(s), wherein optionally the capsule comprises gelatin or HPMC. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) that comprise about 4.5 x 10 ¹⁰ total cells of the Veillonella parvula bacteria are contained in a capsule(s), wherein optionally the capsule comprises gelatin or HPMC. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) that comprise about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria are contained in a capsule(s), wherein optionally the capsule comprises gelatin or HPMC. In some embodiments, the Veillonella parvulci bacteria of the mini-tablet are gamma irradiated.

[58] In some embodiments, the pharmaceutical composition comprising Veillonella parvula bacteria is prepared as a powder (e.g. , for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., mini-tablets comprised in a capsule). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the Veillonella parvula bacteria are gamma irradiated.

[59] In some embodiments, the Veillonella parvula strain is a strain comprising at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Veillonella parvula strain A (ATCC Deposit Number PTA- 125691). In some embodiments, the Veillonella parvula strain is the Veillonella parvula strain A (ATCC Deposit Number PTA- 125691).

[60] In some aspects, the disclosure provides use of the anti-inflammatory bacteria such as a Veillonella parvula strain provided herein and/or a pharmaceutical composition (e.g., a pharmaceutical composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for the preparation of a medicament for the performance of a therapeutic method provided herein. In some aspects, the disclosure provides the antiinflammatory bacteria such as a Veillonella parvula strain provided herein and/or a pharmaceutical composition (e.g., a pharmaceutical composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for use in the performance of a therapeutic method provided herein.

[61] In some embodiments, the methods provided herein further comprise administering to the subject an additional therapy. In some embodiments, the additional therapy comprises the standard of care for the disease being treated (e.g., an inflammatory condition). In some embodiments, the additional therapy is administered at a lower dose than the dose at which it is administered as a monotherapy. In some embodiments, the methods provided herein further comprise administering to the subject an anti-inflammatory medication. In some embodiments, the method further comprises orally administering an anti-inflammatory agent such as NSAIDs or anti-inflammatory steroids. In some embodiments, the method further comprises administering (e.g., orally or intravenously administering) dexamethasone. In some embodiments, the method further comprises administering a BTK inhibitor such as ibrutinib. In some embodiments, the method further comprises administering a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.

[62] In some embodiments, the method further comprises administering to the subject an antibody specific for IL-6 and/or the IL-6 receptor. In some embodiments, the method comprises administering to the subject tocilizumab (Actemra®). In some embodiments, the method comprises administering to the subject sarilumab (Kevzara®).

BRIEF DESCRIPTION OF THE DRAWINGS

[63] FIG. 1 shows a waterfall plot illustrating the percent change in IL-8 expression by subjects after 28 days of treatment with Prevotella histicola Strain B (right) or placebo (left).

[64] FIG. 2 shows a waterfall plot illustrating the percent change in IL-6 expression by subjects after 28 days of treatment with Prevotella histicola Strain B (right) or placebo (left).

[65] FIG. 3 shows a waterfall plot illustrating the percent change in TNFa expression by subjects after 28 days of treatment with Prevotella histicola Strain B (right) or placebo (left).

[66] FIG. 4 shows a waterfall plot illustrating the percent change in IL- 1 [3 expression by subjects after 28 days of treatment with Prevotella histicola Strain B (right) or placebo (left).

[67] FIG. 5 is two panels showing IFNa (left panel) and IFNp (right panel) levels in spleen cells removed from animals treated with Prevotella histicola Strain B (“Strain B”) or dexamethasone or a combination thereof. The effect of the treatments on virally-induced production of these interferons was mimicked by treating the cells with poly (LC).

[68] FIG. 6 is two panels showing IL6 (left panel) and TNFa (right panel) levels in spleen cells removed from animals treated with Prevotella histicola Strain B (“Strain B”) or dexamethasone or a combination thereof.

[69] FIG. 7 is a graph showing the effects of Prevotella histicola Strain B (“Strain B”) or dexamethasone or a combination thereof on ear inflammation in a KLH DTH model. [70] FIG. 8 is a graph showing inflammation 24 hours after intradermal KLH challenge as determined by measuring basal flow using laser speckle contrast imaging (LCSI) in subjects treated with Prevotella histicola Strain B compared to a pooled placebo group.

[71] FIG. 9 shows a waterfall plot illustrating the percent change in IL-8 expression by subjects after 28 days of treatment with low (IX) dose of Prevotella histicola Strain B (“Strain B”) (middle); high (5X) dose of Prevotella histicola Strain B (right); or placebo (left).

[72] FIG. 10 shows a waterfall plot illustrating the percent change in IL-6 expression by subjects after 28 days of treatment with low (IX) dose of Prevotella histicola Strain B (“Strain B”) (middle); high (5X) dose of Prevotella histicola Strain B (right); or placebo (left).

[73] FIG. 11 shows a waterfall plot illustrating the percent change in TNF-a (TNF- a) expression by subjects after 28 days of treatment with low (IX) dose of Prevotella histicola Strain B (“Strain B”) (middle); high (5X) dose of Prevotella histicola Strain B (right); or placebo (left).

[74] FIG. 12 shows a waterfall plot illustrating the percent change in IFN-g (IFN-y) expression by subjects after 28 days of treatment with low (IX) dose of Prevotella histicola Strain B (“Strain B”) (middle); high (5X) dose of Prevotella histicola Strain B (right); or placebo (left).

[75] FIG. 13 shows a waterfall plot illustrating the percent change in IL-17A expression by subjects after 28 days of treatment with low (IX) dose of Prevotella histicola Strain B (“Strain B”) (middle); high (5X) dose of Prevotella histicola Strain B (right); or placebo (left).

[76] FIG. 14 is a graph showing the effects of Prevotella histicola Strain B or dexamethasone on ear inflammation.

[77] FIGS. 15A and 15B are graphs showing the effects of Prevotella histicola Strain B or dexamethasone on the production of IFNa (FIG. 15 A) and IFNp (FIG. 15B) in a spleen cell stimulation assay.

[78] FIG. 16 is a graph showing the effects of Prevotella histicola Strain B or dexamethasone on the systemic production of interferon-gamma.

[79] FIGS. 17A and 17B are a series of graphs showing the effects of Prevotella histicola Strain B on immune cell subsets. [80] FIG. 18 is a series of graphs showing the effects of Prevotella histicola Strain B on KLH-specific IgG and on peanut-specific IgGl or total IgGl in the peanut allergy model.

[81] FIG. 19 is a series of graphs showing the effects of Prevotella histicola Strain B or a strain of Prevotella melaninogenica (“genus Ctrl”) on IFNy response from CD8 T cells to CEF viral peptides as compared to the DC-CD8 T cell co-culture control.

[82] FIGS. 20A- 20C are a series of graphs showing the effects of Veillonella parvula strain A- G.I. on ear inflammation (FIG. 20A) and the effects of Veillonella parvula strain A- G.I. on the production of IFNa (FIG. 20B) and IFNp (FIG. 20C) in a spleen cell stimulation assay.

[83] FIG. 21 is a graph showing the effects of Veillonella parvula strain A- G.I. on the systemic production of interferon-gamma (IFNy).

[84] FIGS. 22A and 22B are a series of graphs showing the effects of Veillonella parvula strain A- G.I. on immune cell subsets.

[85] FIG. 23 is a graph showing the effects of Veillonella parvula strain A- G.I. on KLH-specific IgG in a KLH delayed-type hypersensitivity model.

[86] FIG. 24 is a graph showing the effects of Veillonella parvula strain A- G.I. on IFNy response from CD8 T cells to CEF viral peptides as compared to the DC-CD8 T cell coculture control.

[87] FIG. 25 is a graph showing the ability of Prevotella histicola Strain B to resolve ongoing inflammation rather than suppress the ability of the immune system to respond to later induction of inflammation.

[88] FIGS. 26A and 26B are graphs showing the duration of the effect of Prevotella histicola Strain B on inhibition of inflammation. FIG. 26A shows the effects of Prevotella histicola Strain B on ear inflammation after challenge on Day 8. FIG. 26B shows the effects of Prevotella histicola Strain B on ear inflammation after challenge on Day 23.

DETAILED DESCRIPTION

General

[89] Inflammation is present in many diseases, acute and chronic. Uncontrolled inflammation is a significant cause of pathology and morbidity.

[90] Current anti-inflammatory agents can cause suppression of Type I IFN response, yet preservation of Type I IFN response is important for host anti-viral response. [91] Type I IFN have important anti-inflammatory functions in promoting immune homeostasis. See, e.g.: Perry, et al., Cell Research 15:407-422 (2005); Teijaro, Current Opinion Virology 16:31-40 (2016); Oh et al, Cancer Immunology Res. 7:584-599 (2019).

[92] Defective Type I IFN immune response is associated with exacerbated COVID 19 inflammatory response. See, e.g., Hadjadj et al., Science 369: 718-724 (2020).

[93] Reduced Type I IFN signaling results in delayed virus clearance, enhanced neutrophil infiltration. See, e.g., Channappanavar et al, J. Clin. Investigation 129:3625-3639 (2019).

[94] Unexpectedly, bacteria (e.g, anti-inflammatory bacteria) that have antiinflammatory effects but do not cause suppression of Type I IFN response are being developed. This new class of anti-inflammatory agent can produce functional resolution (partial or complete) of inflammation without the adverse side effects (such as suppression of Type I IFN response) associated with current anti-inflammatories. This new class of antiinflammatory agent can induce physiological processes of inflammation resolution rather than suppressing mediators of inflammation. This class of agent can be used alone or in combination with other anti-inflammatory agents (e.g., which can be administered in lower doses than when used alone) to attain beneficial effects with reduced adverse side effects.

[95] Treatment with anti-inflammatory bacteria, such as Prevotella histicola Strain B, can lead to a prolonged pharmacodynamic effect, which is maintained in the absence of continuous dosing, as compared to a systemic immuno-suppressive drug such as dexamethasone, which requires continuous dosing to maintain its anti-inflammatory effect.

[96] In certain aspects, provided herein is a method of resolving an immune response, comprising administering to the subject an anti-inflammatory bacteria (e.g., a composition, e.g., a pharmaceutical composition containing the anti-inflammatory bacteria). Anti-inflammatory bacteria can be identified using methods disclosed herein (e.g., by determining whether they reduce (e.g., significantly reduce) the levels of a pro-inflammatory cytokine such as IL-8, IL-6, IL-1J3, and/or TNFa in an assay described herein). In some embodiments, the anti-inflammatory bacteria are a. Prevotella histicola strain. In some embodiments, the anti-inflammatory bacteria are a Prevotella histicola strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella histicola strain is administered in a pharmaceutical composition (e.g., pharmaceutical composition and/or a solid dosage form). In some embodiments, the Prevotella histicola strain is Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the anti-inflammatory bacteria are a Veillonella parvula strain. In some embodiments, the anti-inflammatory bacteria are a Veillonella parvula strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of Veillonella parvula strain A (ATCC Deposit Number PTA-125691). In some embodiments, the Veillonella parvula strain is administered in a pharmaceutical composition (e.g., pharmaceutical composition and/or a solid dosage form). In some embodiments, the Veillonella parvula strain is Veillonella parvula strain A (ATCC Deposit Number PTA- 125691). In some embodiments, the Veillonella parvula strain is gamma irradiated. In some embodiments, the pharmaceutical composition comprises one anti-inflammatory strain. In some embodiments, the pharmaceutical composition comprises one strain of bacteria, wherein the strain is an anti-inflammatory strain.

[97] The pharmacodynamic effect of a non-live Prevotella histicola Strain B pharmaceutical composition is through interactions with the immune cells within the small intestine and has no systemic absorption. These local interactions in the small intestine then downregulate systemic inflammation. It has not been observed to colonize or persist in the gut or to affect the microbiome. In clinical studies to date it has been well tolerated, with a side-effect profile indistinct from placebo.

[98] The non-live Prevotella histicola Strain B pharmaceutical composition has demonstrated anti-inflammatory activity with excellent safety and tolerability in three clinical cohorts. One was a human volunteer immunopharmacology study of delayed-type hypersensitivity, which was a formal proof of mechanism for the effect of targeting the small intestinal axis in humans. The other two were cohorts of psoriasis patients which showed both benefits on skin lesions and down-regulation of systemic production of inflammatory cytokines. In preclinical and clinical studies, Prevotella histicola Strain B dampens multiple pathways of inflammation with a placebo-like safety profile. In preclinical studies, it has antiinflammatory efficacy similar to dexamethasone but with the additional benefit of having no negative impact on Type 1 Interferons required for host anti-viral response.

[99] The inflammatory control afforded by targeting the small intestinal axis appears to result in the coordinated down regulation of multiple inflammatory pathways without immunosuppression, mimicking the body’s normal physiological processes of inflammation resolution.

[100] The inflammatory control mechanisms of small intestinal axis lead to inflammation resolution which restores non-inflamed homeostasis without inducing frank immunosuppression. It does this by coordinately down-regulating multiple inflammatory pathways including those which have been validated with targeted antibody therapies, but without the side effects seen with combinations of antibodies or broadly acting oral kinase inhibitors.

[101] In vitro studies of Prevotella histicola Strain B in human and mouse cellular assays and in vivo models support its use in the treatment of immunoinflammatory diseases, including psoriasis. Prevotella histicola Strain B increases secretion of anti-inflammatory cytokines from human immune cells, such as interleukin (IL)- 10 and IL-27, while inducing minimal production of pro-inflammatory cytokines such as IL-6, tumor necrosis factor (TNF) and interferon gamma (IFNy).

[102] In preclinical models, anti-inflammatory bacteria such as the Prevotella histicola Strain B are at least as effective as antibodies and oral drugs. Functional inflammatory resolution without complete suppression in both mice and humans is seen.

[103] Oral administration of Prevotella histicola Strain B to mice led to striking therapeutic effects on delayed-type hypersensitivity (DTH), imiquimod-induced skin inflammation, fluorescein isothiocyanate (FITC) cutaneous hypersensitivity, collagen- induced arthritis (CIA), and experimental acute encephalomyelitis (EAE) in-vivo models. This consistency of effect and dose shows that Prevotella histicola Strain B is coordinately resolving systemic inflammation across TH1, TH2 and TH 17 pathways. This suggests the potential for clinical benefit across multiple conditions and populations. No potentially related adverse effects were seen in the animals used in these experiments with daily dosing for up to 3 weeks, or alternate day dosing for over 7 weeks. Ex vivo immunophenotyping in these models shows increased regulatory T cell numbers and regulatory dendritic cells (DCs) in spleen and mesenteric lymph nodes, as well as decreases in pro-inflammatory cytokines such as IL-23p40, IL- 17, and IL- 13. Prevotella histicola Strain B does not suppress the expression of Type 1 interferons in these ex vivo experiments, suggesting that the broad spectrum of anti-inflammatory effects is achieved without damaging mechanisms of immune surveillance critical for avoiding cancers and pathogens. Treatment also led to enhancement of gut intestinal barrier integrity, which is often disrupted in patients with inflammatory diseases.

Definitions

[104] “Administration” broadly refers to a route of administration of a composition to a subject. Examples of routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal) or injection. Administration by injection includes intravenous (IV), intramuscular (IM), intratumoral (IT) and subcutaneous (SC) administration. The pharmaceutical compositions described herein can be administered in any form by any effective route, including but not limited to intratumoral, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, ophthalmic, (intra)nasally, local, non-oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and intrathecal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g, trans- and perivaginally), intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial. In preferred embodiments, the pharmaceutical compositions described herein are administered orally, rectally, intratumorally, topically, intravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously. In preferred embodiments, the pharmaceutical composition or solid dosage form described herein is administered orally.

[105] The term “decrease” or “deplete” or “reduce” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state. Properties that may be decreased include number of immune cells (e.g., of a particular immune cell type), bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites, and level of cytokines (e.g., a pro- inflammatory cytokine).

[106] The term “increase” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10- fold, 100-fold, 10 ^A 3 fold, 10 ^A 4 fold, 10 ^A 5 fold, 10 ^A 6 fold, and/or 10 ^A 7 fold greater after treatment when compared to a pre-treatment state. Properties that may be increased include number of immune cells (e.g., of a particular immune cell type), bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites, and level of cytokines (e.g., a pro- inflammatory cytokine).

[107] The terms “subject” or “patient” refers to any animal. A subject or a patient described as “in need thereof’ refers to one in need of a treatment for a disease. Mammals (i.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents). For example, the subject may be a non-human mammal including but not limited to of a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee. The subject or patient may be healthy, or may be suffering from (or at increased risk of developing) an immune disorder at any developmental stage or from (or at an increased risk of developing) an infection.

[108] ‘Strain” refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species. The genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the absence (“curing”) of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof. Genetic signatures between different strains may be identified by PCR amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome. In the case in which one strain (compared with another of the same species) has gained or lost antibiotic resistance or gained or lost a biosynthetic capability (such as an auxotrophic strain), strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.

[109] As used herein, the term “treating” a disease in a subject or “treating” a subject having or suspected of having a disease refers to subjecting the subject to a pharmaceutical treatment, e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening. For example, “treating” may decrease the level of IL-8, IL-6, IL- 1(3, and/or TNFa in a subject, e.g., as compared to the level prior to treatment; “treating” may prevent an increase (or cause a decrease) in the level of IL-8, IL-6, IL- 1(3, and/or TNFa in a subject as compared to a standard, e.g., as compared to the level prior to treatment; “treating” may decrease a clinical factor, such as a clinical score for a particular disease as compared to a standard, e.g., as compared to the time or duration in a cohort of subjects who did not receive the treatment.

Anti-Inflammatory Bacteria

[HO] Provided herein are methods and compositions related to the use of antiinflammatory bacteria for the resolution of an inflammatory response in a subject. Bacteria are anti-inflammatory, e.g., if the bacteria reduce (e.g., significantly reduce) the levels of a pro-inflammatory cytokine such as IL-8, IL-6, IL- 1 (3, and/or TNFa, e.g., in an assay described herein. In some embodiments, the anti-inflammatory bacteria (e.g., when orally administered) can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, IL-ip, and/or TNFa expression) in a subject, e.g., in myeloid cells of the subject. In some embodiments, the anti-inflammatory bacteria can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, IL- ip, and/or TNFa expression) in an assay described herein. In some embodiments, the antiinflammatory bacteria (e.g., when orally administered) can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, and/or TNFa expression) in a subject, e.g., in myeloid cells of the subject. In some embodiments, the anti-inflammatory bacteria can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, and/or TNFa expression) in an assay described herein. In some embodiments, the anti-inflammatory bacteria (e.g., when orally administered) can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, and/or TNFa expression) in a subject, e.g., in myeloid cells of the subject, but not in T cells of the subject. In some embodiments, the anti-inflammatory bacteria can reduce inflammatory cytokine expression (e.g., IL-8, IL-6, and/or TNFa expression) in an assay described herein, e.g., in ex vivo stimulated myeloid cells but not in ex vivo stimulated T cells. In some embodiments, the antiinflammatory bacteria (e.g., when orally administered) do not reduce (e.g., do not significantly reduce) the Type I interferon response, e.g., does not reduce (e.g., do not significantly reduce) IFNa and/or IFNp levels in a subject. In some embodiments, the antiinflammatory bacteria do not reduce (e.g., do not significantly reduce) the Type I interferon response, e.g., do not reduce (e.g., do not significantly reduce) IFNa and/or IFNp levels in an assay described herein. In some embodiments, the anti-inflammatory bacteria (e.g., when orally administered) do not reduce (e.g., do not significantly reduce) IFNa and/or IFNp levels in a subject. In some embodiments, the anti-inflammatory bacteria do not reduce (e.g., do not significantly reduce) IFNa and/or IFNp levels in an assay described herein.

[Hl] Prevotella Histicola. The anti-inflammatory bacteria can be a strain of Prevotella. Anti-inflammatory strains of Prevotella can be identified using methods disclosed herein (e.g., by determining whether they reduce (e.g., significantly reduce) the levels of a pro-inflammatory cytokine such as IL-8, IL-6, IL-ip, and/or TNFa in an assay described herein). In some embodiments, the Prevotella strain is a strain of Prevotella histicola. In some embodiments, the Prevotella strain is Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella strain is a strain comprising at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic, 16S or CRISPR nucleotide sequence) of Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella strain is Prevotella histicola Strain B (NRRL accession number B 50329).

[112] Under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purpose of Patent Procedure, the Prevotella histicola Strain B was deposited on October 11, 2018, with the American Type Culture Collection (ATCC) of 10801 University Boulevard, Manassas, Va. 20110-2209 USA and was assigned ATCC Accession Number PTA-125368.

[113] Applicant represents that the ATCC is a depository affording permanence of the deposit and ready accessibility thereto by the public if a patent is granted. All restrictions on the availability to the public of the material so deposited will be irrevocably removed upon the granting of a patent. The material will be available during the pendency of the patent application to one determined by the Commissioner to be entitled thereto under 37 CFR 1.14 and 35 U.S.C. 122. The deposited material will be maintained with all the care necessary to keep it viable and uncontaminated for a period of at least five years after the most recent request for the furnishing of a sample of the deposited plasmid, and in any case, for a period of at least thirty (30) years after the date of deposit or for the enforceable life of the patent, whichever period is longer. Applicant acknowledges its duty to replace the deposit should the depository be unable to furnish a sample when requested due to the condition of the deposit.

[114] Prevotella histicola Strain B can be cultured according to methods known in the art. For example, Prevotella histicola can be grown in ATCC Medium 2722, ATCC Medium 1490, or other medium using methods disclosed, for example in Caballero et al., 2017. “Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium” Cell Host & Microbe 21:592-602, which is hereby incorporated by reference in its entirety.

[115] Veillonella Parvula: Anti-inflammatory strains of Veillonella Parvula can be identified using methods disclosed herein (e.g., by determining whether they reduce (e.g., significantly reduce) the levels of a pro-inflammatory cytokine such as IE-8, IL-6, IL- 1(3, and/or TNFa in an assay described herein). In some embodiments, the Veillonella parvula is Veillonella parvula strain A (ATCC Deposit Number PTA-125691) (also referred to as "Veillonella parvula strain A”). In some embodiments, the Veillonella parvula strain is a strain comprising at least at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Veillonella parvulci strain A (ATCC Deposit Number PTA- 125691).

[116] Under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purpose of Patent Procedure, the Veillonella parvula strain A was deposited on January 25, 2019, with the American Type Culture Collection (ATCC) of 10801 University Boulevard, Manassas, Va. 20110-2209 USA and was assigned ATCC Accession Number PTA- 125691.

[117] Applicant represents that the ATCC is a depository affording permanence of the deposit and ready accessibility thereto by the public if a patent is granted. All restrictions on the availability to the public of the material so deposited will be irrevocably removed upon the granting of a patent. The material will be available during the pendency of the patent application to one determined by the Commissioner to be entitled thereto under 37 CFR 1.14 and 35 U.S.C. 122. The deposited material will be maintained with all the care necessary to keep it viable and uncontaminated for a period of at least five years after the most recent request for the furnishing of a sample of the deposited plasmid, and in any case, for a period of at least thirty (30) years after the date of deposit or for the enforceable life of the patent, whichever period is longer. Applicant acknowledges its duty to replace the deposit should the depository be unable to furnish a sample when requested due to the condition of the deposit.

[118] Veillonella parvula strain A can be cultured according to methods known in the art. For example, Veillonella parvula strain A can be grown under anaerobic conditions in PM1 l+5g/U Na-U-lactate liquid medium supplemented with 0.05g/U FeSC>4, and 0.5 g/L U- cysteine-HCU as reducing agent at 37 degrees C.

[119] In some embodiments, the bacterial compositions comprise whole Veillonella parvula bacteria (e.g., live bacteria, killed bacteria, attenuated bacteria).

[120] In some embodiments, the bacterial compositions comprise whole Veillonella parvula bacteria (e.g., gamma irradiated bacteria).

Pharmaceutical Compositions

[121] In certain embodiments, provided herein are pharmaceutical compositions (e.g., solid dosage forms) comprising anti-inflammatory bacteria. [122] In some embodiments, the pharmaceutical composition comprises one antiinflammatory strain of bacteria.

[123] In some embodiments, the pharmaceutical composition comprises one strain of bacteria, wherein the strain is an anti-inflammatory strain.

[124] In some embodiments, the pharmaceutical composition is formulated as a solid dose (e.g., solid dosage) form, such as a capsule or a tablet. In some embodiments, the pharmaceutical composition comprises an enteric coating or micro encapsulation. In some embodiments, the pharmaceutical composition is prepared as a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the pharmaceutical composition is prepared as a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coating allows release of the pharmaceutical composition in the small intestine, e.g., in the upper small intestine, e.g., in the duodenum.

[125] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3 x IO ¹⁰ to about 1.5 x 10 ¹² total cells of the anti-inflammatory bacteria. In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10 ¹⁰ to about 1.3 x 10 ¹² total cells of the anti-inflammatory bacteria. In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the anti-inflammatory bacteria.

[126] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.

[127] In some embodiments, a dose of anti-inflammatory bacteria of about 3 x IO ¹⁰ to about 1.5 x 10 ¹² total cells are administered (e.g., are for administration) per day. In some embodiments, a dose of anti-inflammatory bacteria of about 8 x IO ¹⁰ to about 1.3 x 10 ¹² total cells are administered (e.g., are for administration) per day. In some embodiments, a dose of anti-inflammatory bacteria of about 4.5 x IO ¹⁰ to about 1.5 x 10 ¹² total cells are administered (e.g., are for administration) per day.

[128] In some embodiments, the pharmaceutical composition comprising antiinflammatory bacteria is prepared as a powder (e.g. , for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g. , mini-tablets comprised in a capsule). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[129] In some embodiments, the solid dosage form is a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 18mm in diameter (size refers to size prior to application of enteric coat). In some embodiments, the anti-inflammatory bacteria in the tablet are lyophilized.

[130] In some embodiments, the solid dosage form is a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the enteric coated capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule. In some embodiments, the anti-inflammatory bacteria in the capsule are lyophilized. In some embodiments, the capsule comprises gelatin. In some embodiments, the capsule comprises HPMC.

[131] In certain embodiments, provided herein are solid dosage forms comprising the anti-inflammatory bacteria. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, the enteric coating comprises a polymethacrylate -based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1: 1) (such as Kollicoat MAE 100P or Eudragit L30-D55).

[132] In some embodiments, the pharmaceutical compositions comprise whole antiinflammatory bacteria such as Prevotella histicola (e.g., live bacteria, killed bacteria, attenuated bacteria).

[133] In some embodiments, the pharmaceutical compositions comprise live antiinflammatory bacteria such as Prevotella histicola bacteria.

[134] In some embodiments, the pharmaceutical compositions comprise viable antiinflammatory bacteria such as Prevotella histicola bacteria.

[135] In certain embodiments, the pharmaceutical compositions comprise non-viable anti-inflammatory bacteria such as Prevotella histicola bacteria.

[136] In some embodiments, the Prevotella histicola is Prevotella histicola Strain B (NRRL accession number B 50329). In some embodiments, the Prevotella histicola strain is a strain comprising at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella histicola Strain B.

[137] In some embodiments, the pharmaceutical composition comprises about 50 mg to about 3 g of Prevotella histicola.

[138] In some embodiments, the pharmaceutical composition comprises about 55mg, about 550 mg, or about 2.76 g of Prevotella histicola.

[139] In some embodiments, the pharmaceutical composition comprises about 2xlO ¹⁰ , 2.1xlO ¹⁰ , 2.2xlO ¹⁰ , 2.3xlO ¹⁰ , 2.4xlO ¹⁰ , 2.5xlO ¹⁰ , 2.6xlO ¹⁰ , 2.7xlO ¹⁰ , 2.8xlO ¹⁰ , 2.9xlO ¹⁰ , 3xlO ¹⁰ , 3. IxlO ¹⁰ , 3.2xlO ¹⁰ , 3.3xlO ¹⁰ , 3.4xlO ¹⁰ , 3.5xlO ¹⁰ , 3.6xlO ¹⁰ , 3.7xlO ¹⁰ , 3.8xlO ¹⁰ , 3.9xlO ¹⁰ , 4xlO ¹⁰ , 5xlO ¹⁰ , 6xlO ¹⁰ , 7xlO ¹⁰ , 8xlO ¹⁰ , 9xlO ¹⁰ , IxlO ¹¹ , 1.1x10“, 1.2x10“, 1.3x10“, 1.4x10“, 1.5x10“, 1.6x10“, 1.7x10“, 1.8x10“, 1.9x10“, 2x10“, 2.1x10“, 2.2x10“, 2.3x10“, 2.4x10“, 2.5x10“, 2.6x10“, 2.7x10“, 2.8x10“, 2.9x10“, 3x10“, 3.1x10“, 3.2x10“, 3.3x10“, 3.4x10“, 3.5x10“, 3.6x10“, 3.7x10“, 3.8x10“, 3.9x10“, 4x10“ 5x10“, 6x10“, 7x10“, 8x10“, 9x10“, IxlO ¹² , 1.5xl0 ¹² total cells e revotella histicola. In some embodiments, the pharmaceutical composition comprises about 8xl0 ¹⁰ total cells of Prevotella histicola. In some embodiments, the pharmaceutical composition comprises about 1.6x10“ total cells Prevotella histicola. In some embodiments, the pharmaceutical composition comprises about 8x10“ total cells of Prevotella histicola.

Herein, total cells is determined by total cell count (e.g., determined by Coulter counter).

[140] In some embodiments, the pharmaceutical composition comprises at least about 2xlO ¹⁰ , 2. IxlO ¹⁰ , 2.2xlO ¹⁰ , 2.3xlO ¹⁰ , 2.4xlO ¹⁰ , 2.5xlO ¹⁰ , 2.6xlO ¹⁰ , 2.7xlO ¹⁰ , 2.8xlO ¹⁰ , 2.9xlO ¹⁰ , 3xl0 ¹⁰ , 3. IxlO ¹⁰ , 3.2xlO ¹⁰ , 3.3xl0 ¹⁰ , 3.4xlO ¹⁰ , 3.5xl0 ¹⁰ , 3.6xlO ¹⁰ , 3.7xlO ¹⁰ , 3.8xl0 ¹⁰ , 3.9xlO ¹⁰ , 4xlO ¹⁰ , 5xl0 ¹⁰ , 6xlO ¹⁰ , 7xlO ¹⁰ , 8xl0 ¹⁰ , 9xlO ¹⁰ , 1x10“, 1.1x10“, 1.2x10“, 1.3x10“, 1.4x10“, 1.5x10“, 1.6x10“, 1.7x10“, 1.8x10“, 1.9x10“, 2x10“, 2.1x10“, 2.2x10“, 2.3x10“, 2.4x10“, 2.5x10“, 2.6x10“, 2.7x10“, 2.8x10“, 2.9x10“, 3x10“, 3.1x10“, 3.2x10“, 3.3x10“, 3.4x10“, 3.5x10“, 3.6x10“, 3.7x10“, 3.8x10“, 3.9x10“, 4x10“ 5x10“, 6x10“, 7x10“, 8x10“, 9x10“, IxlO ¹² , 1.5 xlO ¹² total cells of Prevotella histicola.

[141] In some embodiments, the pharmaceutical composition comprises at most about 2xlO ¹⁰ , 2. IxlO ¹⁰ , 2.2xlO ¹⁰ , 2.3xlO ¹⁰ , 2.4xlO ¹⁰ , 2.5xlO ¹⁰ , 2.6xlO ¹⁰ , 2.7xlO ¹⁰ , 2.8xlO ¹⁰ , 2.9xlO ¹⁰ , 3xl0 ¹⁰ , 3. IxlO ¹⁰ , 3.2xlO ¹⁰ , 3.3xl0 ¹⁰ , 3.4xlO ¹⁰ , 3.5xl0 ¹⁰ , 3.6xlO ¹⁰ , 3.7xlO ¹⁰ , 3.8xl0 ¹⁰ , 3.9xlO ¹⁰ , 4xlO ¹⁰ , 5xl0 ¹⁰ , 6xlO ¹⁰ , 7xlO ¹⁰ , 8xl0 ¹⁰ , 9xlO ¹⁰ , 1x10“, 1.1x10“, 1.2x10“, 1.3x10“, 1.4x10“, 1.5x10“, 1.6x10“, 1.7x10“, 1.8x10“, 1.9x10“, 2x10“, 2.1x10“, 2.2xlO ⁿ , 2.3x10“, 2.4x10“, 2.5x10“, 2.6x10“, 2.7x10“, 2.8x10“, 2.9x10“, 3x10“, 3.1x10“, 3.2x10“, 3.3x10“, 3.4x10“, 3.5x10“, 3.6x10“, 3.7x10“, 3.8x10“, 3.9x10“, 4x10“ 5x10“, 6x10“, 7x10“, 8x10“, 9x10“, IxlO ¹² , 1.5 xlO ¹² total cells of Prevotella histicola.

[142] In some embodiments, the pharmaceutical composition comprises about 50 mg to about 3 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[143] In some embodiments, the pharmaceutical composition comprises about 55mg, about 550 mg, or about 2.76 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[144] In some embodiments, the pharmaceutical composition comprises about 2xlO ¹⁰ , 2.1xlO ¹⁰ , 2.2xlO ¹⁰ , 2.3xlO ¹⁰ , 2.4xlO ¹⁰ , 2.5xlO ¹⁰ , 2.6xlO ¹⁰ , 2.7xlO ¹⁰ , 2.8xlO ¹⁰ , 2.9xlO ¹⁰ , 3xl0 ¹⁰ , 3. IxlO ¹⁰ , 3.2xlO ¹⁰ , 3.3xl0 ¹⁰ , 3.4xlO ¹⁰ , 3.5xl0 ¹⁰ , 3.6xlO ¹⁰ , 3.7xlO ¹⁰ , 3.8xl0 ¹⁰ , 3.9xlO ¹⁰ , 4xlO ¹⁰ , 5xl0 ¹⁰ , 6xlO ¹⁰ , 7xlO ¹⁰ , 8xl0 ¹⁰ , 9xlO ¹⁰ , 1x10“, 1.1x10“, 1.2x10“, 1.3x10“, 1.4x10“, 1.5x10“, 1.6x10“, 1.7x10“, 1.8x10“, 1.9x10“, 2x10“, 2.1x10“, 2.2x10“, 2.3x10“, 2.4x10“, 2.5x10“, 2.6x10“, 2.7x10“, 2.8x10“, 2.9x10“, 3x10“, 3.1x10“, 3.2x10“, 3.3x10“, 3.4x10“, 3.5x10“, 3.6x10“, 3.7x10“, 3.8x10“, 3.9x10“, 4x10“ 5x10“, 6x10“, 7x10“, 8x10“, 9x10“, IxlO ¹² , 1.5xl0 ¹² total cells e revotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 8xl0 ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 1.6x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 3.2x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 6.4x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 8x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 9.6x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 12.8x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 16x10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ to about 1.6 x 10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ to about 16 x 10“ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 8 x IO ¹⁰ to about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹⁰ to about 1.6 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹¹ to about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 9.6 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 9.6 x 10 ¹¹ to about 12.8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the pharmaceutical composition comprises about 12.8 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. Herein, total cells is determined by total cell count (e.g., determined by Coulter counter).

[145] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[146] In some embodiments, the pharmaceutical composition comprises about 8 x

10 ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[147] In some embodiments, the pharmaceutical composition comprises about 1.6 x

10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[148] In some embodiments, the pharmaceutical composition comprises about 3.2 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[149] In some embodiments, the pharmaceutical composition comprises about 6.4 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[150] In some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹¹ total cells oiPrevotella histicola, e.g., of Prevotella Strain B 50329.

[151] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ to about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[152] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹⁰ to about 1.6 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[153] In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 ¹¹ to about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[154] In some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹⁰ to about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. [155] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x IO ¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[156] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[157] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[158] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[159] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[160] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[161] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[162] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 16 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[163] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. [164] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10 ¹¹ to about 12.8 x 10 ¹¹ total cells oiPrevotella histicola, e.g., of Prevotella Strain B 50329.

[165] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10 ¹¹ to about 16 x 10 ¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[166] In some embodiments, the pharmaceutical composition comprising Prevotella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., mini-tablets comprised in a capsule). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[167] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.

[168] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹⁰ total cells.

[169] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO ¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 ¹⁰ total cells.

[170] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 ¹¹ total cells. [171] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ⁿ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 ⁿ total cells. For clarity, about 3.2 x 10 ¹¹ total cells includes total cell counts within ±5% of 3.2 x 10 ¹¹ total cells e.g., 3.35 x 10 ¹¹ total cells.

[172] In some embodiments, the pharmaceutical composition is prepared as a solid dosage form. In certain embodiments, provided herein are solid dosage forms comprising the Prevotella histicola bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, each tablet comprises about 8 x IO ¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each tablet comprises about 1.6 x 10 ¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each tablet comprises about 3.2 x 10 ¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x 10 ¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 1.6 x 10 ¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 3.2 x 10 ¹¹ total cells of the Prevotella histicola bacteria.

[173] In some embodiments, the pharmaceutical composition, e.g., pharmaceutical composition is a powder. The powder can be resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage or a food), e.g., for administration to a subject.

[174] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x IO ¹⁰ total cells are administered (e.g., are for administration) per day.

[175] In some embodiments, a dose of Prevotella histicola bacteria of about 1.6 x 10 ¹¹ total cells are administered (e.g., are for administration) per day.

[176] In some embodiments, a dose of Prevotella histicola bacteria of about 3.2 x IO ¹¹ total cells are administered (e.g., are for administration) per day.

[177] In some embodiments, a dose of Prevotella histicola bacteria of about 6.4 x 10 ¹¹ total cells are administered (e.g., are for administration) per day.

[178] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x 10 ¹¹ total cells are administered (e.g., are for administration) per day.

[179] In some embodiments, a dose of Prevotella histicola bacteria of about 9.6 x 10 ¹¹ total cells are administered (e.g., are for administration) per day.

[180] In some embodiments, a dose of Prevotella histicola bacteria of about 12.8 x 10 ¹¹ total cells are administered (e.g., are for administration) per day. [181] In some embodiments, a dose of Prevotella histicola bacteria of about 16 x 10 ¹¹ total cells are administered (e.g., are for administration) per day.

[182] In some embodiments, the solid dosage form is a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 18mm in diameter (size refers to size prior to application of enteric coat). In some embodiments, the tablet comprises about 8 x 10 ¹⁰ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 1.6 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 3.2 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[183] In some embodiments, the solid dosage form is a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the enteric coated capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule. In some embodiments, the capsule comprises about 8 x 10 ¹⁰ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 1.6 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 3.2 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the capsule are lyophilized. In some embodiments, the capsule comprises gelatin. In some embodiments, the capsule comprises HPMC.

[184] In certain embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, the enteric coating comprises a polymethacrylate -based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1: 1) (such as Kollicoat MAE 100P or Eudragit L30-D55).

[185] In some embodiments, each tablet comprises about 8 x 10 ¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 8 x 10 ¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 8 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 8 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 8 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 8 x IO ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[186] In some embodiments, each tablet comprises about 1.6 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 1.6 x 10 ¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 1.6 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 1.6 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 1.6 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[187] In some embodiments, each tablet comprises about 3.2 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 3.2 x 10 ¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[188] In some embodiments, each capsule comprises about 1.6 x 10 ¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x 10 ¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[189] In some embodiments, each capsule comprises about 8 x 10 ¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 8 x 10 ¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. . In some embodiments, 5 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 8 x 10 ¹⁰ total cells) are administered, e.g., once or twice daily to a subject. [190] In some embodiments, each capsule comprises about 1.6 x 10 ⁿ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x 10 ¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[191] In some embodiments, each capsule comprises about 3.2 x 10 ¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 3.2 x 10 ¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 3.2 x 10 ⁿ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 3.2 x 10 ¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[192] In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Prevotella bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. [193] In some embodiments, at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,

50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella strain. 10%, 15%, 20%, 25%, 30%, 35%,

40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or

99% of the bacteria in the composition are of the Prevotella strain. In some embodiments, at least 99% of the bacteria in the composition are of the Prevotella strain. In some embodiments, the bacteria in the composition are essentially (e.g., about 100%) of the Prevotella strain.

[194] In some embodiments, about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%,

11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%,

27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%,

43%. 440 450 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%,

59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%,

75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the protein in the pharmaceutical composition is Prevotella strain bacteria protein.

[195] In some embodiments, the pharmaceutical compositions comprise whole Veillonella parvula bacteria (e.g., live bacteria, killed bacteria, attenuated bacteria). In some embodiments, the Veillonella parvula bacteria is non-viable. In some embodiments, the Veillonella parvula bacteria has been gamma irradiated (e.g., according to a method described herein). In some embodiments, the Veillonella parvula bacteria is live.

[196] In some embodiments, the pharmaceutical composition comprises only one strain of bacteria, e.g., Veillonella parvula.

[197] In some embodiments, the Veillonella parvula is Veillonella parvula strain A (ATCC Deposit Number PTA-125691). In some embodiments, the Veillonella parvula strain is a strain comprising at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Veillonella parvula strain A (ATCC Deposit Number PTA-125691).

[198] In some embodiments, the pharmaceutical compositions comprise whole Veillonella parvula bacteria (e.g., live bacteria, killed bacteria, attenuated bacteria). [199] In some embodiments, the pharmaceutical compositions comprise whole Veillonella parvulci bacteria (e.g., gamma irradiated bacteria).

[200] In certain embodiments, the pharmaceutical compositions (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1 x IO ¹⁰ total cells, about 2 x IO ¹⁰ total cells, about 3 x IO ¹⁰ total cells, about 4 x IO ¹⁰ total cells, about 4.5 x IO ¹⁰ total cells, about 5 x IO ¹⁰ total cells, about 6 x IO ¹⁰ total cells, about 7 x IO ¹⁰ total cells, about 8 x 10 ¹⁰ total cells, about 9 x 10 ¹⁰ total cells, about 1 x 10 ¹¹ total cells, about 1.5 x 10 ¹¹ total cells, about 2 x 10 ¹¹ total cells, about 3 x 10 ¹¹ total cells, about 4 x 10 ¹¹ total cells, about 5 x 10 ¹¹ total cells, about 6 x 10 ¹¹ total cells, about 7 x 10 ¹¹ total cells, about 7.5 x 10 ¹¹ total cells, about 8 x 10 ¹¹ total cells, about 9 x 10 ¹¹ total cells, about 1 x 10 ¹² total cells, about 1.5 x 10 ¹² total cells, about 2 x 10 ¹² total cells of the Veillonella parvula bacteria.

[201] In certain embodiments, the pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises at least 1 x 10 ¹⁰ total cells (e.g., at least 1 x 10 ¹⁰ total cells, at least 2 x 10 ¹⁰ total cells, at least 3 x 10 ¹⁰ total cells, at least 4 x 10 ¹⁰ total cells, at least 4.5 x 10 ¹⁰ total cells, at least 5 x 10 ¹⁰ total cells, at least 6 x 10 ¹⁰ total cells, at least 7 x 10 ¹⁰ total cells, at least 8 x 10 ¹⁰ total cells, at least 9 x 10 ¹⁰ total cells, at least 1 x 10 ¹¹ total cells, at least 1.5 x 10 ¹¹ total cells, at least 2 x 10 ¹¹ total cells, at least 3 x

10 ¹¹ total cells, at least 4 x 10 ¹¹ total cells, at least 5 x 10 ¹¹ total cells, at least 6 x 10 ¹¹ total cells, at least 7 x 10 ¹¹ total cells, at least 7.5 x 10 ¹¹ total cells, at least 8 x 10 ¹¹ total cells, at least 9 x 10 ¹¹ total cells, at least 1 x 10 ¹² total cells, at least 1.5 x 10 ¹² total cells, at least 2 x

10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical compositions comprises about 7.5 x 10 ¹¹ total cells the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ¹² total cells the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 3 x 10 ¹⁰ to about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 4.5 x 10 ¹⁰ to about 1.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ⁿ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 1.5 x 10 ⁿ to about 7.5 x 10 ¹¹ total cells of the Veillonella parvula bacteria. In some embodiments, the pharmaceutical composition comprises about 7.5 x 10 ¹¹ to about 1.5 x 10 ¹² total cells of the Veillonella parvula bacteria.

[202] In some embodiments, at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Veillonella parvula strain. 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Veillonella parvula strain. In some embodiments, at least 99% of the bacteria in the composition are of the Veillonella parvula strain. In some embodiments, the bacteria in the composition are essentially (e.g., about 100%) of the Veillonella parvula strain.

[203] In some embodiments, about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%,

11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%,

27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%,

43%. 440 450 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%,

59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%,

75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the protein in the pharmaceutical composition is Veillonella parvula strain bacteria protein.

[204] In some embodiments, the pharmaceutical composition is formulated as a capsule or a tablet or a mini-tablet. In some embodiments, the pharmaceutical composition comprises an enteric coating or micro encapsulation. In some embodiments, the capsule is an enteric coated capsule.

[205] In some embodiments, to quantify the numbers of anti-inflammatory bacteria such as Prevotella histicola or Veillonella parvula bacteria present in a bacterial sample, electron microscopy (e.g., EM of ultrathin frozen sections) can be used to visualize the bacteria and count their relative numbers. Alternatively, combinations of nanoparticle tracking analysis (NTA), Coulter counting, and dynamic light scattering (DLS) or a combination of these techniques can be used. NTA and the Coulter counter count particles and show their sizes. DLS gives the size distribution of particles, but not the concentration. Bacteria frequently have diameters of 1-2 um. The full range is 0.2-20 um. Combined results from Coulter counting and NTA can reveal the numbers of bacteria in a given sample. Coulter counting reveals the numbers of particles with diameters of 0.7-10 um. NTA reveals the numbers of particles with diameters of 50-1400 nm. For most bacterial samples, the Coulter counter alone can reveal the number of bacteria in a sample. In some embodiments, total cells (total cell count) is determined by Coulter counting.

[206] In some embodiments, the anti-inflammatory bacteria may be quantified based on total cells, e.g., total cell count (TCC) (e.g., determined by Coulter counter).

[207] In certain aspects, provided are pharmaceutical compositions for administration subjects. In some embodiments, the pharmaceutical compositions are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format. In some embodiments, the pharmaceutical compositions is combined with an adjuvant such as an immuno-adjuvant (e.g., STING agonists, TLR agonists, NOD agonists).

[208] In some embodiments the composition comprises at least one carbohydrate. A “carbohydrate” refers to a sugar or polymer of sugars. The terms “saccharide,” “polysaccharide,” “carbohydrate,” and “oligosaccharide” may be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule. Carbohydrates generally have the molecular formula CnFhnOn. A carbohydrate may be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide. The most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two joined monosaccharides. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose. Typically, an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates may contain modified saccharide units such as 2 ’-deoxyribose wherein a hydroxyl group is removed, 2 ’-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N- acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2 ’-fluororibose, deoxyribose, and hexose). Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.

[209] In some embodiments the composition comprises at least one lipid. As used herein a “lipid” includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans). In some embodiments the lipid comprises at least one faty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16: 1), margaric acid (17:0), heptadecenoic acid (17: 1), stearic acid (18:0), oleic acid (18: 1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20: 1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EP A), docosanoic acid (22:0), docosenoic acid (22: 1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and tetracosanoic acid (24:0). In some embodiments the composition comprises at least one modified lipid, for example a lipid that has been modified by cooking.

[210] In some embodiments the composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.

[2H] In some embodiments the composition comprises at least one supplemental vitamin. The at least one vitamin can be fat-soluble or water-soluble vitamins. Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin.

[212] In some embodiments the composition comprises an excipient. Non-limiting examples of suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.

[213] In some embodiments the excipient is a buffering agent. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

[214] In some embodiments the excipient comprises a preservative. Non-limiting examples of suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.

[215] In some embodiments the composition comprises a binder as an excipient. Non-limiting examples of suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.

[216] In some embodiments the composition comprises a lubricant as an excipient. Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[217] In some embodiments the composition comprises a dispersion enhancer as an excipient. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.

[218] In some embodiments the composition comprises a disintegrant as an excipient. In some embodiments the disintegrant is a non-effervescent disintegrant. Nonlimiting examples of suitable non-effervescent disintegrants include starches such as com starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth. In some embodiments the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.

[219] In some embodiments, the composition is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed. Specific examples of the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, capsules, liquids, pastes, and jellies.

[220] In some embodiments the composition is a food product for animals, including humans. The animals, other than humans, are not particularly limited, and the composition can be used for various livestock, poultry, pets, experimental animals, and the like. Specific examples of the animals include pigs, cattle, horses, sheep, goats, chickens, wild ducks, ostriches, domestic ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like, but the animals are not limited thereto.

Solid Dosage Form Composition

[221] In certain embodiments, provided herein are solid dosage forms comprising anti-inflammatory bacteria and a pharmaceutically acceptable carrier.

[222] In certain embodiments, provided herein are solid dosage forms comprising anti-inflammatory bacteria such as a Prevotella strain such as a strain of Prevotella histicola such as Prevotella histicola Strain B (NRRL accession number B 50329), and a pharmaceutically acceptable carrier.

[223] In certain embodiments, provided herein are solid dosage forms comprising anti-inflammatory bacteria such as a Veillonella parvula strain such as a strain of Veillonella parvula such as Veillonella parvula strain A (ATCC Deposit Number PTA-125691), and a pharmaceutically acceptable carrier.

[224] In some embodiments, the solid dosage form described herein can be a capsule, e.g., an enteric coated capsule. In some embodiments, the capsule is enteric coated, e.g., for duodenal release at pH 5.5. The capsule can be, e.g., a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule. In some embodiments, the capsule comprises freeze-dried powder that comprises the antiinflammatory bacteria such as the Prevotella strain. In some embodiments, the capsule comprises freeze-dried powder that comprises the anti-inflammatory bacteria such as the Veillonella parvula strain. [225] In some embodiments, the solid dosage form described herein can be, e.g., a tablet or a mini-tablet. In some embodiments, a plurality of mini-tablets can be in (e.g. , loaded into) a capsule.

[226] In some embodiments, the solid dosage form comprises a tablet (> 4mm) (e.g., 5mm-17mm). For example, the tablet is a 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm or 18mm tablet.

[227] In some embodiments, the solid dosage form comprises a mini-tablet. The mini-tablet can be in the size range of lmm-4 mm range. E.g., the mini-tablet can be a 1mm mini-tablet, 1.5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet.

[228] The mini-tablets can be in a capsule. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule that contains the mini -tablets can comprise a single layer coating, e.g., a non-enteric coating such as HPMC (hydroxyl propyl methyl cellulose) or gelatin. The mini-tablets can be inside a capsule: the number of minitablets inside a capsule will depend on the size of the capsule and the size of the mini -tablets. As an example, a size 0 capsule can contain 31-35 (an average of 33) mini-tablets that are 3mm mini -tablets.

[229] The solid dosage form (e.g., tablet or mini-tablet) described herein can be enterically coated.

Additional Therapy

[230] In some embodiments, an additional therapy is administered to the subject. In some embodiments, the additional therapy comprises an anti-inflammatory agent such as NSAIDs or anti-inflammatory steroids. In some embodiments, the additional therapy comprises dexamethasone. In some embodiments, the additional therapy is administered at a lower dose than the dose at which it is administered as a monotherapy. In some embodiments, the methods provided herein further comprise administering to the subject an anti-inflammatory agent. In some embodiments, the method further comprises orally administering an anti-inflammatory agent such as an NSAID or an anti-inflammatory steroid. In some embodiments, the method further comprises administering (e.g., orally or intravenously administering) dexamethasone.

[231] In some embodiments, the additional therapy comprises an antibody specific for IL-6 and/or the IL-6 receptor. In some embodiments, the additional therapy comprises tocilizumab (Actemra®). In some embodiments, the additional therapy comprises sarilumab (Kevzara®). [232] In some embodiments, the additional therapy can comprise an anti-inflammatory therapy. For example, the anti-inflammatory therapy can comprise a corticosteroid; sirolimus; anakinra; filamod; or an antibody. In some embodiments, the antibody can comprise a GMSF inhibitor, such as lenzilumab or gimsilumab; an anti -IL 1 beta inhibitor such as canakinumab; an IL-6 inhibitor such as tocilizumab or siltuximab; an IL-6R inhibitor such as sarilumab; and/or a CCR5 antagonist such as leronlimab.

[233] In some embodiments, the additional therapy can comprise a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.

[234] In some embodiments, the additional therapy can comprise a BTK inhibitor such as ibrutinib.

Administration

[235] In certain aspects, provided herein is a method of delivering a pharmaceutical composition described herein to a subject. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

[236] In some embodiments, the pharmaceutical composition is administered orally. In some embodiments, the administration to the subject for a single day followed by a washout period before the next dose. In some embodiments, the washout period is at least 12 hours, 24 hours, 36 hours, 48 hours, 50 hours, 60 hours, or 72 hours.

[237] In some embodiments, the pharmaceutical composition is administered after the washout period once daily for 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days.

[238] In some embodiments, the pharmaceutical composition is administered after the washout period twice daily for 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days.

[239] In some embodiments, the pharmaceutical composition is administered for 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days.

[240] In some embodiments, the pharmaceutical composition is administered twice daily for 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days.

[241] In some embodiments, the pharmaceutical composition is administered once daily for 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days.

[242] In some embodiments, the pharmaceutical composition is administered twice daily for 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days.

[243] In some embodiments, the pharmaceutical composition is administered once daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the pharmaceutical composition is administered once daily for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the pharmaceutical composition is administered once daily for at least 8 weeks. In some embodiments, the pharmaceutical composition is administered once daily for at least 12 weeks. In some embodiments, the pharmaceutical composition is administered once daily for at least 16 weeks.

[244] In some embodiments, the pharmaceutical composition is administered twice daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the pharmaceutical composition is administered twice daily for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the pharmaceutical composition is administered twice daily for at least 8 weeks. In some embodiments, the pharmaceutical composition is administered twice daily for at least 12 weeks. In some embodiments, the pharmaceutical composition is administered twice daily for at least 16 weeks.

[245] In some embodiments, the pharmaceutical composition is administered twice daily for three days and then once daily for the remainder of the treatment (e.g., until day 14).

[246] In some embodiments, the pharmaceutical composition is formulated as a capsule (e.g. containing mini-tablets or powder) or a tablet. In some embodiments, the bacterial formulation comprises an enteric coating or micro encapsulation. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the capsule is an HPMC capsule. In some embodiments, the capsule is a gelatin capsule.

[247] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. [248] In some embodiments of the methods provided herein, the pharmaceutical composition is administered in conjunction with the administration of an additional therapeutic. In some embodiments, the pharmaceutical composition comprises antiinflammatory bacteria such as Prevotella histicola or Veillonella parvulci bacteria coformulated with the additional therapeutic. In some embodiments, the pharmaceutical composition is co-administered with the additional therapeutic. In some embodiments, the additional therapeutic is administered to the subject before administration of the pharmaceutical composition (e.g, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours before, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days before). In some embodiments, the additional therapeutic is administered to the subject after administration of the pharmaceutical composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours after, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days after). In some embodiments the same mode of delivery are used to deliver both the pharmaceutical composition and the additional therapeutic. In some embodiments different modes of delivery are used to administer the pharmaceutical composition and the additional therapeutic. For example, in some embodiments the pharmaceutical composition is administered orally while the additional therapeutic is administered via injection (e.g., an intravenous, and/or intramuscular injection).

[249] In some embodiments, the pharmaceutical composition is administered orally. In some embodiments, the administration to the subject for a single day followed by an interval period before the next dose. In some embodiments, the interval period is at least 3 days, 4 days, 5 days, 6 days, or 7 days.

[250] In some embodiments, the pharmaceutical composition is administered after the interval period once daily for 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, or 28 days.

[251] In some embodiments, the pharmaceutical composition is formulated as a capsule or a tablet. In some embodiments, the bacterial formulation comprises an enteric coating or micro encapsulation. In some embodiments, the capsule is an enteric coated capsule.

[252] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. [253] In certain embodiments, the pharmaceutical compositions, dosage forms, and kits described herein can be administered in conjunction with any other conventional treatment. These treatments may be applied as necessary and/or as indicated and may occur before, concurrent with or after administration of the pharmaceutical compositions, dosage forms, and kits described herein.

[254] The dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the particular microorganism to be administered, duration and route of administration, the kind and stage of the disease, and other compounds such as drugs being administered concurrently. In addition to the above factors, such levels can be affected by the infectivity of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art. In the present methods, appropriate minimum dosage levels of microorganisms can be levels sufficient for the microorganism to survive, grow and replicate. The dose of the pharmaceutical compositions described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, the degree or stage of a target disease, and the like. For example, the general effective dose of the agents may range between 0.01 mg/kg body weight/day and 1000 mg/kg body weight/day, between 0.1 mg/kg body weight/day and 1000 mg/kg body weight/day, 0.5 mg/kg body weight/day and 500 mg/kg body weight/day, 1 mg/kg body weight/day and 100 mg/kg body weight/day, or between 5 mg/kg body weight/day and 50 mg/kg body weight/day. The effective dose may be 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 mg/kg body weight/day or more, but the dose is not limited thereto.

[255] In some embodiments, the dose administered to a subject is sufficient to prevent disease (e.g., autoimmune disease, inflammatory disease, metabolic disease), delay its onset, or slow or stop its progression. One skilled in the art will recognize that dosage will depend upon a variety of factors including the strength of the particular compound employed, as well as the age, species, condition, and body weight of the subject. The size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect.

[256] Suitable doses and dosage regimens can be determined by conventional rangefinding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. An effective dosage and treatment protocol can be determined by routine and conventional means, starting e.g., with a low dose in laboratory animals and then increasing the dosage while monitoring the effects, and systematically varying the dosage regimen as well. Animal studies are commonly used to determine the maximal tolerable dose ("MID") of bioactive agent per kilogram weight. Those skilled in the art regularly extrapolate doses for efficacy, while avoiding toxicity, in other species, including humans.

[257] In accordance with the above, in therapeutic applications, the dosages of the active agents used in accordance with the invention vary depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage.

[258] Separate administrations can include any number of two or more administrations, including two, three, four, five or six administrations. One skilled in the art can readily determine the number of administrations to perform or the desirability of performing one or more additional administrations according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein. Accordingly, the methods provided herein include methods of providing to the subject one or more administrations of a pharmaceutical composition, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results.

[259] The time period between administrations can be any of a variety of time periods. The time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response and/or the time period for a subject to clear the bacteria from normal tissue. In one example, the time period can be a function of the time period for a subject to mount an immune response; for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be less than the time period for a subject to mount an immune response, such as less than about one week, less than about ten days, less than about two weeks, or less than about a month. In another example, the time period can be a function of the time period for a subject to clear the bacteria from normal tissue; for example, the time period can be more than the time period for a subject to clear the bacteria from normal tissue, such as more than about a day, more than about two days, more than about three days, more than about five days, or more than about a week.

[260] In some embodiments, the delivery of an additional therapeutic in combination with the pharmaceutical composition described herein reduces the adverse effects and/or improves the efficacy of the additional therapeutic.

[261] The effective dose of an additional therapeutic described herein is the amount of the therapeutic agent that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, with the least toxicity to the patient. The effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. In general, an effective dose of an additional therapy will be the amount of the therapeutic agent which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.

[262] The toxicity of an additional therapy is the level of adverse effects experienced by the subject during and following treatment. Adverse events associated with additional therapy toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylasix, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery disease, cataracts, central neurotoxicity, cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspepsia, dyspnea, edema, electrolyte imbalance, esophagitis, fatigue, loss of fertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytopenia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, hearing loss, heart failure, heart palpitations, heartbum, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylasemia, hypercalcemia, hyperchloremia, hyperglycemia, hyperkalemia, hyperlipasemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, impotence, infection, injection site reactions, insomnia, iron deficiency, itching, joint pain, kidney failure, leukopenia, liver dysfunction, memory loss, menopause, mouth sores, mucositis, muscle pain, myalgias, myelosuppression, myocarditis, neutropenic fever, nausea, nephrotoxicity, neutropenia, nosebleeds, numbness, ototoxicity, pain, palmar-plantar erythrodysesthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonia, pneumonitis, proteinuria, pulmonary embolus, pulmonary fibrosis, pulmonary toxicity, rash, rapid heartbeat, rectal bleeding, restlessness, rhinitis, seizures, shortness of breath, sinusitis, thrombocytopenia, tinnitus, urinary tract infection, vaginal bleeding, vaginal dryness, vertigo, water retention, weakness, weight loss, weight gain, and xerostomia. In general, toxicity is acceptable if the benefits to the subject achieved through the therapy outweigh the adverse events experienced by the subject due to the therapy.

[263] In certain embodiments, the therapeutic effects of these orally delivered medicines come from their action on pattern recognition receptors on immune cells in the lining of the small intestine. These cells, in turn, modulate immune cells circulating throughout the body. The medicines are microbes, but do not target the microbiome. In some embodiments, monoclonal microbials do not colonize or persist in the gut and do not modify the colonic microbiome. In some embodiments, they are gut-restricted.

[264] In certain embodiments, the methods provided herein result in change (e.g., an increase or a decrease) in serum and/or expression levels of one or more cytokines (or one or more cellular factors) after the subject is treated according to a method provided herein for a set time interval as compared to before treatment and/or at the onset of treatment. In certain embodiments, the one or more cytokines include TNF-a, IL-ip, IL-6, and IL-8. In some embodiments, the time interval is up to 28 days. In certain embodiments, the time interval is about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, about 18 days, about 19 days, about 20 days, about 21 days, about 22 days, about 23 days, about 24 days about 25 days, about 26 days, about 27 days, and/or about 28 days. Subjects

[265] In certain embodiments, the methods provided herein resolve inflammation in a subject in need thereof (e.g., as compared to a standard). In some embodiments, the subject in need thereof suffers from an IL-8, IL-6, IL- 1 P, and/or TNFa mediated disease or condition.

[266] In certain aspects, provided herein is a method of resolving an inflammatory response in a subject in need thereof, wherein the method dampens (e.g., reduces) the production of IL-6, IL-8 and/or TNFa from myeloid cells.

[267] In certain aspects, provided herein is a method of resolving an inflammatory response in a subject in need thereof, wherein the method dampens (e.g., reduces) the production of IL-6, IL-8 and/or TNFa from myeloid cells but not from T-cells.

[268] In certain aspects, provided herein is a method of resolving an inflammatory response in a subject in need thereof, wherein a Type I interferon (IFN) response is not reduced, e.g., as determined by IFNa or IFNp levels.

[269] In certain aspects, provided herein is a method of resolving an inflammatory response in a subject in need thereof, wherein IFNa and/or IFNp levels are not reduced.

[270] In some embodiments, the subject in need thereof has an infection, e.g., a viral infection.

[271] In some embodiments, the subject in need thereof is a child (e.g., a child of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 years old). In certain embodiments, the subject is an infant of no more than 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 months old.

[272] In certain embodiments, the subject is an older adult. In certain embodiments, the subject is at least 50, 55, 60, 65, 70, 75, 80, 80, or 90 years old.

[273] In some embodiments, the subject is a pregnant woman. In some embodiments, the subject is a woman of child-bearing age.

[274] In certain embodiments, the subject is immunocompromised (e.g., a subject who has undergone radiation therapy, immunotherapy, has received a transplant, is taking anti-rejection medication, is taking immunosuppressant medication, is infected with HIV, etc.).

Additional Cellular Factors

[275] As described herein, the pharmaceutical compositions and methods provided herein can be used to reduce inflammatory cytokine expression (e.g., IL-8, IL-6, IL-ip, and/or TNFa expression) in a subject. For example, the pharmaceutical compositions and methods provided herein can be used to treat diseases and conditions associated therewith.

[276] The pharmaceutical compositions and methods provided herein can be used to reduce the level of IL-8, IL-6, IL-1J3, and/or TNFa. The pharmaceutical compositions and methods provided herein can be used to reduce the level of IL-8, IL-6, and/or TNFa from myeloid cells. The pharmaceutical compositions and methods provided herein can be used to reduce the level of IL-8, IL-6, and/or TNFa from myeloid cells, but not from T cells.

Disorders Associated with Inflammation

[277] In some embodiments, the methods and pharmaceutical compositions described herein relate to the treatment or prevention of a disease or disorder associated with inflammation. In some embodiments, the disease or disorder is an inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis). In some embodiments, the disease or disorder is psoriasis. In some embodiments, the disease or disorder is atopic dermatitis. In some embodiments, the disease or disorder is an infection, e.g., a viral infection.

[278] The methods described herein can be used to treat any subject in need thereof. As used herein, a “subject in need thereof’ includes any subject that has inflammation, as well as any subject with an increased likelihood of acquiring a such a disease or disorder. The subject may have had an appropriate inflammatory response, such as an immune response, but the subject may be in need to treatment to resolve the inflammation.

[279] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with an autoimmune disease, such as chronic inflammatory bowel disease, systemic lupus erythematosus, psoriasis, muckle-wells syndrome, rheumatoid arthritis, multiple sclerosis, or Hashimoto's disease; an allergic disease, such as a food allergy, pollenosis, or asthma; an infectious disease, such as an infection with Clostridium difficile,' an inflammatory disease such as a TNF-mediated inflammatory disease (e.g., an inflammatory disease of the gastrointestinal tract, such as pouchitis, a cardiovascular inflammatory condition, such as atherosclerosis, or an inflammatory lung disease, such as chronic obstructive pulmonary disease); a pharmaceutical composition for suppressing rejection in organ transplantation or other situations in which tissue rejection might occur; a supplement, food, or beverage for improving immune functions; or a reagent for suppressing the proliferation or function of immune cells. [280] In some embodiments, the methods provided herein are useful for the treatment of inflammation. In certain embodiments, the inflammation of any tissue and organs of the body, including musculoskeletal inflammation, vascular inflammation, neural inflammation, digestive system inflammation, ocular inflammation, inflammation of the reproductive system, and other inflammation, as discussed below.

[281] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with an immune disorder of the musculoskeletal system. Immune disorders of the musculoskeletal system include, but are not limited, to those conditions affecting skeletal joints, including joints of the hand, wrist, elbow, shoulder, jaw, spine, neck, hip, knew, ankle, and foot, and conditions affecting tissues connecting muscles to bones such as tendons. Examples of such immune disorders, which may be treated with the methods and compositions described herein include, but are not limited to, arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis fibrosa cystic).

[282] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with an ocular immune disorder. Ocular immune disorders refers to an immune disorder that affects any structure of the eye, including the eyelids. Examples of ocular immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry eye), scleritis, trichiasis, and uveitis

[283] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with nervous system immune disorders. Examples of nervous system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, encephalitis, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis and schizophrenia. [284] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with the vasculature or lymphatic system. Examples of inflammation of the vasculature or lymphatic system which may be treated with the methods and compositions described herein include, but are not limited to, arthrosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis.

[285] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with digestive system immune disorders. Examples of digestive system immune disorders which may be treated with the methods and pharmaceutical compositions described herein include, but are not limited to, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, and proctitis. Inflammatory bowel diseases include, for example, certain art- recognized forms of a group of related conditions. Several major forms of inflammatory bowel diseases are known, with Crohn's disease (regional bowel disease, e.g., inactive and active forms) and ulcerative colitis (e.g., inactive and active forms) the most common of these disorders. In addition, the inflammatory bowel disease encompasses irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis. Other less common forms of IBD include indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD- associated dysplasia, dysplasia associated masses or lesions, and primary sclerosing cholangitis.

[286] The pharmaceutical compositions described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) inflammation associated with reproductive system immune disorders. Examples of reproductive system immune disorders which may be treated with the methods and pharmaceutical compositions described herein include, but are not limited to, cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvodynia.

[287] The methods and pharmaceutical compositions described herein may be used to treat autoimmune conditions having an inflammatory component. Such conditions include, but are not limited to, acute disseminated alopecia universalise, Behcet's disease, Chagas' disease, chronic fatigue syndrome, dysautonomia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type 1, type 2 diabetes, giant cell arteritis, goodpasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch-Schonlein purpura, Kawasaki's disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, Muckle-Wells syndrome, multiple sclerosis, myasthenia gravis, opsoclonus myoclonus syndrome, optic neuritis, ord's thyroiditis, pemphigus, polyarteritis nodosa, polymyalgia, rheumatoid arthritis, Reiter's syndrome, Sjogren's syndrome, temporal arteritis, Wegener's granulomatosis, warm autoimmune haemolytic anemia, interstitial cystitis, Lyme disease, morphea, psoriasis, sarcoidosis, scleroderma, ulcerative colitis, and vitiligo.

[288] The methods and pharmaceutical compositions described herein may be used to treat T-cell mediated hypersensitivity diseases having an inflammatory component. Such conditions include, but are not limited to, contact hypersensitivity, contact dermatitis (including that due to poison ivy), uticaria, skin allergies, respiratory allergies (hay fever, allergic rhinitis, house dustmite allergy) and gluten-sensitive enteropathy (Celiac disease).

[289] Other immune disorders which may have an inflammatory component and may be treated with the methods and pharmaceutical compositions include, for example, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, iritis, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, parotitis, percarditis, peritonoitis, pharyngitis, pleuritis, pneumonitis, prostatistis, pyelonephritis, and stomatisi, transplant rejection (involving organs such as kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small bowel, skin allografts, skin homografts, and heart valve xengrafts, sewrum sickness, and graft vs host disease), acute pancreatitis, chronic pancreatitis, acute respiratory distress syndrome, Sexary's syndrome, congenital adrenal hyperplasis, nonsuppurative thyroiditis, hypercalcemia associated with cancer, pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme, exfoliative dermatitis, seborrheic dermatitis, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, drug hypersensistivity reactions, allergic conjunctivitis, keratitis, herpes zoster ophthalmicus, iritis and oiridocyclitis, chorioretinitis, optic neuritis, symptomatic sarcoidosis, fulminating or disseminated pulmonary tuberculosis chemotherapy, idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) haemolytic anemia, regional enteritis, autoimmune vasculitis, multiple sclerosis, chronic obstructive pulmonary disease, solid organ transplant rejection, sepsis. Preferred treatments include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, Type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, chronic obstructive pulmonary disease, and inflammation accompanying infectious conditions (e.g., sepsis).

EXAMPLES

Example 1 : Prevotella histicola Strain B in healthy participants and participants with mild to moderate psoriasis or mild to moderate atopic dermatitis

[290] Prevotella histicola Strain B (NRRL accession number B 50329) has recently completed a series of cohorts in a phase lb study in human volunteers and patients with psoriasis.

[291] The primary endpoints were safety and tolerability. Prevotella histicola Strain B (NRRL accession number B 50329) has a placebo-like profile, consistent with the lack of systemic absorption. There was no persistence beyond the 28-day daily dosing period and no modification of the colonic microbiome by 16S RNA sequencing of patient stool samples.

[292] Two cohorts of patients with mild-to -moderate psoriasis were treated with a low dose (1.6xlO ⁿ cells per day) and high dose (8xl0 ⁿ cells per day) of Prevotella histicola Strain B (NRRL accession number B 50329) daily for 28 days. The lower dose was estimated by allometric scaling of the just-maximally effective dose in mouse inflammation models. The high dose was 5X higher.

[293] Whole blood samples were obtained from each subject. A whole blood stimulation assay was performed using sub-optimal LPS stimulus. Fresh sodium heparin anticoagulated bloods were collected from 12 subjects and couriered at ambient temperature. On receipt of samples, the blood was used to set up the following conditions: (a) Unstimulated and (b) LPS stimulated (10 ng/ml) at 24 h.

[294] After incubation, plasma was isolated by centrifugation and stored at -80°C. All stored samples were evaluated for IL-6, IL-1J3, IL-8, TNFa, IL-10, and IFNy using Luminex. A total of four Luminex assays were performed. All samples from a single subject were run together on the same Luminex assay plate to avoid inter-assay variation when comparing baseline and last-dose samples. Waterfall plots illustrating the percent change in IL-6, IL-1J3, IL-8, TNFa cytokine expression by subjects after 28 days of treatment with Prevotella histicola Strain B (right) or placebo (left) are provided in FIGS. 1-4. Similar results were not seen for IL- 10 or IFNy. Example 2: Combination study of Prevotella histicola Strain B and dexamethasone in a therapeutic dosing model

[295] Dexamethose is a corticosteroid often used in the treatment of many inflammatory and autoimmune conditions, including rheumatic diseases, skin diseases, severe allergies, and asthma. While systemic dexamethasone is efficacious in many of these diseases, corticosteroids exert effects on most of the body's systems (heart, immune, muscles and bones, endocrine and nervous system), and therefore chronic treatment with dexamethasone can result in a number of undesirable side effects, including aggression, anxiety, insomnia, weight gain, diarrhea, muscle wasting, and fatigue. In addition, because dexamethasone is a broad immune-suppressive drug, it may inhibit the production of protective immune responses, such as the secretion of Type 1 interferons that are critical in anti-viral responses. A study was performed to understand how Prevotella histicola Strain B compares to systemic dexamethasone as individual treatments, or in combination, in reduction of inflammation and the impact on pro-inflammatory cytokines as well as Type 1 interferons. This study was also performed with a short course (3 days) of dosing in a therapeutic regimen, starting 6 days after the KLH sensitization

[296] Evidence for the lack of immunosuppression comes from effects on type 1 interferons, as shown in FIG. 5. Spleen cells were removed from animals treated with Prevotella histicola Strain B or dexamethasone. The effect of the treatments on virally- induced production of interferons was mimicked by treating the cells with poly (EC), an analog of double-stranded RNA. Prevotella histicola Strain B had no effect on IFNa (IFNa) or IFNb (IFNP), unlike dexamethasone which suppressed both, even at this sub-therapeutic dose. It was notable that while dexamethasone significantly inhibited the production of interferon-alpha (IFNa) and interferon-beta (IFNP) in the spleen cell stimulation assay (FIG. 5), Prevotella histicola Strain B mono-therapy had no impact on these Type 1 interferons. This demonstrates that Prevotella histicola Strain B can selectively inhibit inflammation and pro-inflammatory cytokines, while preserving protective Type 1 interferon responses.

[297] The combination significantly reduced the production of IL-6 and TNFa from spleen cells (FIG. 6).

[298] Three days of dosing with Prevotella histicola Strain B, one of two doses of dexamethasone, and the combination of Prevotella histicola Strain B with dexamethasone all inhibited ear inflammation (FIG. 7). A dose-response relationship was seen with dexamethasone, and the combination of Prevotella histicola Strain B with the lower 0. 1 mg/kg dose of dexamethasone was more efficacious than either Prevotella histicola Strain B or 0.1 mg/kg dexamethasone alone. This result suggests that Prevotella histicola Strain B may increase the efficacy of lower doses of corticosteroids, resulting in the reduction of the undesirable side effects associated chronic steroid use.

[299] Methods: Mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On Day 6 after the sensitization, mice were dosed for 3 days with oral Prevotella histicola Strain B, dexamethasone (0. 1 mg/kg or 0.4 mg/kg) given intraperitoneally, or a combination of Prevotella histicola Strain B and dexamethasone. On day 8, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge. For the ex vivo cytokine analysis, spleen cells from treated mice were incubated for 48 hours in vitro and stimulated with either LPS or polyinosinic-polycytidylic acid (poly I:C), a potent ligand for Toll-like receptor 3, which induces interferon-alpha (IFNa) and interferon-beta (IFNp )from immune cells.

Example 3: Prevotella histicola Strain B immunopharmacology study

[300] An immunopharmacology study using an antigen challenge method to demonstrate the anti-inflammatory effects of Prevotella histicola Strain B was performed. Twelve volunteers were immunized with keyhole limpet hemocyanin (KLH) and treated with Prevotella histicola Strain B daily for 28 days. Inflammation 24 hours after intradermal KLH challenge was determined by measuring basal blood flow at the site of the intradermal challenge using laser speckle contrast imaging. A group of 20 placebo subjects was also tested as part of a range of conditions examined. Prevotella histicola Strain B reduced basal blood flow to a level close to the pre-challenge baseline, which is similar to the effects seen in the equivalent preclinical model in mice.

[301] The study evaluated the effect of Prevotella histicola Strain B on the immune response to KLH challenge, using laser speckle contrast imaging, circulating cytokines, and other measures of inflammatory response.

[302] In cohort 1, twelve volunteers were immunized with KLH and treated with Prevotella histicola Strain B (8. Ox 10 ^{1 1} cells once daily) for 28 days using the powder-in- capsule formulation. Inflammation 24 hours after intradermal KLH challenge was determined by measuring basal flow using laser speckle contrast imaging (LCSI). FIG. 8 shows the effects of Prevotella histicola Strain B compared to a pooled placebo group (24 volunteers). Prevotella histicola Strain B reduced basal blood flow close to the pre-challenge baseline, comparable to the effects seen in the equivalent DTH preclinical mouse model.

Example 4: Prevotella histicola Strain B in healthy participants and participants with mild to moderate psoriasis or mild to moderate atopic dermatitis

[303] As described in Example 1, Prevotella histicola Strain B (NRRL accession number B 50329) has recently completed a series of cohorts in a phase lb study in human volunteers and patients with psoriasis.

[304] Two cohorts of patients with mild-to -moderate psoriasis were treated with a low dose (1.6xlO ⁿ cells per day) and high dose (8xl0 ⁿ cells per day) of Prevotella histicola Strain B (NRRL accession number B 50329) daily for 28 days.

[305] Whole blood samples were obtained from each subject and whole blood stimulation assays were performed.

[306] Effects on biomarkers of systemic inflammation were measured by ex vivo stimulation of whole blood samples taken from patients at baseline and after 28 days of treatment.

[307] Two stimulation conditions were used on whole blood samples taken at day 28:

• LPS stimulation for the effect of Prevotella histicola Strain B on inflammatory cytokines from myeloid cells.

• CD3/CD28 stimulation for the effect of Prevotella histicola Strain B on inflammatory cytokines from T-cells.

[308] Treatment with Prevotella histicola Strain B dampened the production of IL-6, IL- 8 and TNFa from myeloid cells but not from T-cells.

• Reductions in inflammatory biomarkers were observed in both cohorts of psoriasis patients

• No patient showed spikes of excess production of these inflammatory cytokines after treatment with Prevotella histicola Strain B

• Prevotella histicola Strain B appears to work by inducing physiological processes of inflammation resolution rather than by suppressing mediators of inflammation

[309] As shown in the waterfall plots of FIGS. 9-13, Prevotella histicola Strain B (Strain B) treatment does not significantly impact production of the measured cytokines by CD3/CD28 stimulation of whole blood from psoriasis patients. Waterfall plots are percent change from baseline to day 28. Samples from patients treated with a low (IX) dose (1.6xlO ⁿ cells per day) and high (5X) dose (8xl0 ⁿ cells per day) of Prevotella histicola Strain B (NRRL accession number B 50329) daily for 28 days were analyzed. FIG. 9 shows the levels of IL-8. FIG. 10 shows the levels of IL-6. FIG. 11 shows the levels of TNF-a. FIG. 12 shows the levels of IFN-g. FIG. 13 shows the levels of IL-17A.

Example 5: Prevotella histicola Strain B effects on inflammation without impacting innate and adaptive immune responses that mediate host anti-viral responses

[310] Antiviral responses are activated rapidly after viral infection in order to control and prevent dissemination of the virus. Virus infection results in two general types of immune response. The first is a rapid-onset innate immune response against the virus, which involves the synthesis of Type 1 interferons and the stimulation of Natural Killer (NK) cells. If the infection proceeds beyond the first few rounds of viral replication, the innate immune response will trigger the adaptive immune response. The adaptive immune response itself has two components, the humoral response (the synthesis of virus-specific immunoglobulins by B lymphocytes) and the cell-mediated response (the synthesis of specific CD8+ cytotoxic T lymphocytes that kill infected cells through secretion of interferon gamma (IFNy)). Both of these components of the adaptive immune response result also in the production of long-lived memory cells that allow for a much more rapid response to a subsequent infection with the same virus. Thus, an immune competent host should be able to mount both an innate and adaptive immune response.

[3H] In the studies presented in this Example, Prevotella histicola Strain B is administered orally and is gut-restricted. Therefore, Prevotella histicola Strain B exerts its anti-inflammatory effects on peripheral tissue through engagement of cells of the intestine, including small intestinal epithelial cells and immune cells in the lamina propria.

[312] Prevotella histicola Strain B has been shown in preclinical mouse inflammation models to reduce inflammation-related antigen-specific T cell responses, without impacting innate and adaptive immune responses that mediate host anti-viral responses. This is demonstrated by:

• Intact anti-viral TLR3 -mediated Type 1 interferon (alpha and beta) response

• Normal interferon-gamma (IFNy) production by immune cells

• Full complement of immune cell subsets (absolute number and percentage), including CD8 T lymphocytes, B lymphocytes, and myeloid lineage cells • No reduction of antigen-specific antibody responses (KLH-specific IgG and total and peanut-specific IgGl)

[313] In human immune cell in vitro assays, Prevotella histicola Strain B did not alter the ability of human dendritic cells to induce the production of IFNy from memory CD8 T cells in response to a viral peptide pool (Cytomegalovirus, Epstein-Bar virus, and Influenza virus), an important component of an anti-viral response.

[314] Clinically, treatment with Prevotella histicola Strain B was shown to reduce specific inflammatory myeloid cell cytokines such as IL-6 and IL-8, while not affecting levels of T cell cytokines such as interferon-gamma, produced by circulating peripheral blood mononuclear cells.

[315] Taken together, the data demonstrate that treatment with Prevotella histicola Strain B does not result in general immuno-suppression of multiple immune pathways but is effective through a selective restoration of immune homeostasis.

[316] TLR3 -mediated induction of Type 1 interferons in the KLH delayed-type hypersensitivity model

[317] Emerging data from human studies has identified type 1 interferons as key cytokines that are important in host resistance to SARS-CoV-2 infection and disease severity. Toll-Like Receptor 3 (TLR3) is a receptor expressed by human immune cells that mediates viral recognition, and the subsequent production of Type 1 interferons. Measuring Type 1 interferons from cells stimulated through TLR3 is a way to measure the strength of the antiviral response.

[318] Methods: Mice were immunized by subcutaneous injection with KLH emulsified with Complete Ereund’s Adjuvant. On Day 6 after the sensitization, mice were dosed for 3 days with oral Prevotella histicola Strain B or dexamethasone given intraperitoneally. On day 8, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge. For the ex vivo cytokine analysis, spleen cells from treated mice were incubated for 48 hours in vitro and stimulated with polyinosinic-polycytidylic acid (poly I:C), a molecule that mimics viral double-strained RNA, and a potent ligand for Tolllike receptor 3, which induces interferon-alpha (IFNa) and interferon-beta (IFNP) from immune cells.

[319] Results: Three days of dosing with Prevotella histicola Strain B or dexamethasone significantly inhibited ear inflammation (FIG. 14). In addition, as shown in FIGS. 15A and 15B, while dexamethasone significantly inhibited the production of IFNa (FIG. 15A) and IF p (FIG. 15B) in the spleen cell stimulation assay, oral Prevotella histicola Strain B had no impact on these Type 1 interferons. This demonstrates that Prevotella histicola Strain B selectively inhibits tissue inflammation while preserving protective anti-viral Type 1 interferon responses.

[320] Interferon gamma production by lymphocytes in vivo

[321] Interferon gamma (IFNy) is another cytokine that is important in controlling virus infections. It does this by exerting cellular effects at multiple levels. First, the interaction of IFNy with its receptor and the subsequent induction of a variety of genes and gene products result in the downregulation of virus replication. Additionally, IFNy activates cytokine production by T cells, monocytes, and resident cells, and augments cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell killing by the induction of molecules such as granzyme B or major histocompatibility complex (MHC) class I, and it enhances immune reactivity through the induction of MHC class II molecules. Therefore, another key measure of antiviral competence is the robust production of IFNy.

[322] Methods: In the same study as above, spleen cells were restimulated with PMA and ionomycin. PMA activates protein kinase C, while ionomycin is a calcium ionophore, and stimulation with these compounds bypasses the T cell membrane receptor complex and will lead to activation of several intracellular signaling pathways, resulting in T cell activation and production of a variety of cytokines.

[323] Results: Stimulation with PMA/ionomycin induced robust production of IFNy from spleen cells, and treatment with Prevotella histicola Strain B or dexamethasone did not reduce the systemic production of interferon-gamma, demonstrating that the CTL/NK axis of the anti-viral immune was intact. See FIG. 16.

[324] Immune cell subsets quantification after Prevotella histicola Strain B dosing

[325] In addition to IFN production, a protective immune response to SARS-CoV-2 involves both cell-mediated immunity and antibody production. T-cell responses against the SARS-CoV-2 spike protein have been characterized and correlate well with IgG antibody titers in COVID- 19 patients. CD8+ T cells are the main inflammatory cells and play a vital role in virus clearance. Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells showed a significant association with inflammatory status in COVID- 19, especially CD8+ T cells and CD4+/CD8+ ratio. Decreased CD4+ T cells and CD8+ T cells have been observed in both mild cases and severe cases but accentuated in the severe cases. In multivariate analysis, post-treatment decrease in CD8+ T cells and B cells and increase in were indicated as independent predictors of poor treatment outcome. Therefore, keeping a full complement of immune cells, particularly T and B cells, is important for maintaining viral resistance. Other major cell types that assist in activating the adaptive immune anti-viral response are NK cells, neutrophils, macrophages, and monocytes.

[326] Methods: Mesenteric lymph nodes which drain the small intestine were removed at the end of a delayed-type hypersensitivity study, which was performed as described above. Mesenteric lymph nodes (MLNs) represent peripheral lymphoid tissues in which all the immune cell types reside or traffic through. Therefore, any changes in cell numbers will be reflected in the cell composition of the MLNs. In addition, because the MLNs drain the gut- associated tissues, any changes associated with oral dosing of Prevotella histicola Strain B would likely be observed in the MLNs first. Single cell suspensions were made from the lymph nodes, stained using antibodies against the relevant cell surface markers to identify individual cell types, and quantified by flow cytometry.

[327] Results: Treatment with Prevotella histicola Strain B for 5 days did not alter any immune cell subsets, including T cells, NK cells, B cells, neutrophils, macrophages, and monocytes in the lymph nodes (FIGS. 17A and B). These results demonstrate that Prevotella histicola Strain B does not impact the adaptive arm of the immune system, which indicates that anti-viral T cell and B cell responses will not be reduced after Prevotella histicola Strain B treatment.

[328] In addition to the preclinical data, phenotypic analysis of blood cells from healthy volunteers treated with Prevotella histicola Strain B for 28 days showed that subsets of immune cells in the blood, including regulatory B cells and regulatory T cells were not changed at the end of the study. (Data not shown)

[329] Antigen-specific and total IgG antibody production from two models of skin inflammation

[330] Antibodies are one of the essential features of antigen-triggered adaptive immunity against viruses and requires a coordinated response between antigen-presenting cells such as dendritic cells, antigen-specific helper T cells, and antigen-specific B cells. In preclinical models that use a model antigen such as KLH to induce an immune response, antigen-specific antibodies are also generated. KLH-specific IgG were measured from a DTH study, and total and peanut-specific IgGl were measured from a mouse model of peanut allergy.

[331] Methods: The DTH was performed as described above. Blood was collected at the end of the study for measurement of KLH-specific IgG. For the peanut allergy model, mice were sensitized on the shaved back using light tape stripping to remove the outer dead layers of epidermis followed by application of peanut protein to induce an allergic response to peanut antigen. The tape -stripping and peanut protein application occurred on days 0, 3, and 6. Mice were dosed daily from Day 0 through Day 21. Blood was collected on Day 35 for measurement of peanut-specific and total IgGl .

[332] Results: Although treatment with Prevotella histicola Strain B causes a marked reduction in peripheral inflammation in the KLH delayed-type hypersensitivity model, no reduction of KLH-specific IgG was observed. Similarly, for the peanut allergy model, no differences in peanut-specific or total IgGl were observed after 21 days of Prevotella histicola Strain B dosing. The results are shown in FIG. 18. These data demonstrate that oral dosing of Prevotella histicola Strain B does not impair the antibody response to foreign antigens. These data also correlate well with the observation that Prevotella histicola Strain B did not cause a reduction in B cells or CD4+ T cells, which are required for the generation of an antibody response.

[333] In vitro assay co-culture with human dendritic cells and CD 8 T cells

[334] An in vitro assay with primary human DCs and autologous CD8+ T cells was carried out to measure the capacity of Prevotella histicola Strain B to modulate antigenspecific CD8+ T cell responses.

[335] Methods: Primary human DCs from 3 healthy donors were differentiated in vitro for 7 days. To assess the immuno-modulatory properties of Prevotella histicola Strain B, DCs were incubated with Prevotella histicola Strain B or with a Prevotella melaninogenica strain that does not exhibit anti-inflammatory activity, for 24 hours in vitro. After 24 hours of microbe conditioning, microbes were removed from the DC culture and autologous human CD8+ T cells and CEF Class I peptide pool was added. The CEF peptide pool is composed of peptides from Cytomegalovirus, Epstein Bar virus, and Influenza virus, pathogens to which the majority of the human population has been exposed. After 24 hours of stimulation with CEF peptide, DC-CD8+ T cell supernatants were collected and IFNy was measured.

[336] Results: Incubation with Prevotella histicola Strain B did not inhibit the ability of dendritic cells to induce an IFNy response from CD8 T cells to CEF viral peptides (neither enhanced nor decreased) compared to the DC-CD8 T cell co-culture control. As a genus control, a strain of Prevotella melaninogenica was also tested in the model and induced increased levels of IFNy compared to Prevotella histicola Strain B. Results are shown in FIG. 19. These data demonstrate that Prevotella histicola Strain B does not impair the CD8+ T cell response to viral antigens, nor does it exacerbate the response. [337] Conclusion

[338] The combination of in vitro, in vivo, and ex vivo data demonstrate that Prevotella histicola Strain B does not broadly impair either innate or adaptive immune responses. Prevotella histicola Strain B is orally delivered and gut restricted, and therefore its effect is exerted through local interactions with cells of the small intestine, which are then translated from the gut to the periphery to resolve inflammation. Anti-viral responses such as cytotoxic T cell production of interferon-gamma, innate anti-viral production of interferon-alpha and interferon-beta, and the generation of high affinity antibodies are all preserved after treatment with Prevotella histicola Strain B.

[339] The data demonstrate that treatment with Prevotella histicola Strain B results in resolution of multiple pathways of inflammation without leading to immunosuppression of the host response.

Example 6: Veillonella parvula strain A effects on inflammation without impacting innate and adaptive immune responses that mediate host anti-viral responses

[340] Veillonella parvula strain A- G.I. is a pharmaceutical preparation of a single strain of Veillonella parvula (Veillonella parvula strain A), originally isolated from a fresh ileostomy sample of an IBD patient in remission, which has been gamma-irradiated (G.I.). Veillonella parvula strain A- G.I. is administered orally and is gut-restricted. Therefore, Veillonella parvula strain A- G.I. exerts its anti-inflammatory effects on peripheral tissue through engagement of cells of the intestine, including small intestinal epithelial cells and immune cells in the lamina propria.

[341] Veillonella parvula strain A- G.I. has been shown in preclinical mouse inflammation models to reduce inflammation-related antigen-specific T cell responses, without impacting innate and adaptive immune responses that mediate host anti-viral responses. This is demonstrated by:

• Intact anti-viral TLR3-mediated Type 1 interferon (IFNa and IFNP) response

• Normal interferon-gamma (IFNy) production by immune cells

• Full complement of immune cell subsets (absolute number and percentage), including CD8 T lymphocytes, B lymphocytes, and myeloid lineage cells

No reduction of antigen-specific or total IgG responses after immunization with a model antigen (Keyhole limpet haemocyanin (KLH)) [342] In human immune cell in vitro assays, Veillonella parvula strain A- G.I. did not alter the ability of human dendritic cells to induce the production of IFNg from memory CD 8 T cells in response to a viral peptide pool (Cytomegalovirus, Epstein-Bar virus, and Influenza virus), an important component of an anti-viral response.

[343] Taken together, the data demonstrate that treatment with Veillonella parvula strain A- G.I. does not result in general immuno-suppression of multiple immune pathways but is effective through the selective restoration of immune homeostasis.

[344] TLR3 -mediated induction of Type 1 interferons in the KLH delayed-type hypersensitivity model

[345] Emerging data from human studies has identified Type 1 interferons as key cytokines that are important in host resistance to SARS-CoV-2 infection and disease severity. Toll-Like Receptor 3 (TLR3) is a receptor expressed by human immune cells that mediates viral recognition, and the subsequent production of Type 1 interferons. Measuring Type 1 interferons from cells stimulated through TLR3 is a way to measure the strength of the antiviral response.

[346] Methods: Mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On Day 5 after the sensitization, mice were dosed for 4 days with oral Veillonella parvula strain A- G.I. On day 8, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge. For the ex vivo cytokine analysis, spleen cells from treated mice were incubated for 48 hours in vitro and stimulated with polyinosinic-polycytidylic acid (poly EC), a molecule that mimics viral double-strained RNA, and a potent ligand for Toll-like receptor 3, which induces interferon-alpha (IFNa) and interferon-beta (IFNP) from immune cells.

[347] Results: Four days of dosing with Veillonella parvula strain A- G.I. significantly inhibited ear inflammation (FIG. 20A). In addition, oral Veillonella parvula strain A- G.I. had no impact on the induction of Type 1 interferons IFNa (FIG. 20B) and IFNp (FIG. 20C). This demonstrates that Veillonella parvula strain A- G.I. selectively inhibits tissue inflammation while preserving protective anti-viral Type 1 interferon responses.

[348] Interferon gamma production by lymphocytes in vivo

[349] Interferon gamma (IFNy) is another cytokine that is important in controlling virus infections. It does this by exerting cellular effects at multiple levels. First, the interaction of IFNy with its receptor and the subsequent induction of a variety of genes and gene products result in the downregulation of virus replication. Additionally, IFNy activates cytokine production by T cells, monocytes, and resident cells, and augments cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell killing by the induction of molecules such as granzyme B or major histocompatibility complex (MHC) class I, and it enhances immune reactivity through the induction of MHC class II molecules. Therefore, another key measure of anti-viral competence is the robust production of IFNy.

[350] Methods: In the same study as above, spleen cells were restimulated with PMA and ionomycin. PMA activates protein kinase C, while ionomycin is a calcium ionophore, and stimulation with these compounds bypasses the T cell membrane receptor complex and will lead to activation of several intracellular signaling pathways, resulting in T cell activation and production of a variety of cytokines.

[351] Results: Stimulation with PMA/ionomycin induced robust production of IFNy from spleen cells, and treatment with Veillonella parvula strain A- G.I. did not reduce the systemic production of interferon-gamma, demonstrating that the CTL/NK axis of the anti-viral immune was intact (FIG. 21).

[352] Immune cell subsets quantification after Veillonella parvula strain A- G.I. dosing

[353] In addition to IFN production, a protective immune response to SARS-CoV-2 involves both cell-mediated immunity and antibody production. T cell responses against the SARS-CoV-2 spike protein have been characterised and correlate well with IgG antibody titres in COVID- 19 patients. CD8+ T cells are the main inflammatory cells and play a vital role in virus clearance. Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells showed a significant association with inflammatory status in COVID- 19, especially CD8+ T cells and CD4+/CD8+ ratio. Decreased CD4+ T cells and CD8+ T cells have been observed in both mild cases and severe cases but accentuated in the severe cases. In multivariate analysis, post-treatment decrease in CD8+ T cells and B cells were indicated as independent predictors of poor treatment outcome. Therefore, keeping a full complement of immune cells, particularly T and B cells, is important for maintaining viral resistance. Other major cell types that assist in activating the adaptive immune anti-viral response are neutrophils, macrophages, and monocytes. These immune cell populations were quantified after 5 days of dosing mice with Veillonella parvula strain A- G.I. Lymphocytes are the predominant leukocyte in most strains of healthy wild-type mice, making up 70% to 80% of the white blood cell differential count. Myeloid cells residing in mucosal tissues like the lining of the small intestine form the first defense against pathogens. Lymphocytes were therefore measured in the spleen, which reflects the cellular composition of the blood, and myeloid cells in the mesenteric lymph nodes that drain the small intestine. Because the MLNs drain the gut-associated tissues, any changes associated with oral dosing of Veillonella parvula strain A- G.I. would likely be observed in the MLNs first.

[354] Methods: The spleen and mesenteric lymph nodes which drain the small intestine were removed at the end of a delayed-type hypersensitivity study, which was performed as described above. In this study mice were dosed for 5 days with Veillonella parvula strain A- G.I. by oral gavage. Single cell suspensions were made from the spleen and lymph nodes, stained using antibodies against the relevant cell surface markers to identify individual cell types, and quantified by flow cytometry.

[355] Results: Treatment with Veillonella parvula strain A- G.I. for 5 days did not alter any immune cell subsets, including T cells, B cells, neutrophils, macrophages, and monocytes in the lymph nodes, compared to treatment with vehicle (FIGS. 22A-22B). These results demonstrate that Veillonella parvula strain A- G.I. does not impact the adaptive arm of the immune system, which suggests that anti-viral T cell and B cell responses will not be reduced after Veillonella parvula strain A- G.I. treatment.

[356] Antigen-specific and total IgG antibody production from two models of skin inflammation

[357] Antibodies are one of the essential features of antigen-triggered adaptive immunity against viruses and requires a coordinated response between antigen-presenting cells such as dendritic cells, antigen-specific helper T cells, and antigen-specific B cells. In preclinical models that use a model antigen such as KLH to induce an immune response, antigen-specific antibodies are also generated.

[358] Methods: The DTH was performed as described above. Blood was collected at the end of the study for measurement of total and KLH-specific IgG.

[359] Results: Although treatment with Veillonella parvula strain A- G.I. causes a marked reduction in peripheral inflammation in the KLH delayed-type hypersensitivity model, no reduction of total or KLH-specific IgG was observed (FIG. 23). These data demonstrate that oral dosing of Veillonella parvula strain A- G.I. does not impair the antibody response to foreign antigens. These data also correlate well with the observation that Veillonella parvula strain A- G.I. did not cause a reduction in B cells or CD4+ T cells, which are required for the generation of an antibody response. [360] In vitro assay co-culture with human dendritic cells and CD 8 T cells

[361] An in vitro assay with primary human DCs and autologous CD8+ T cells was carried out to measure the capacity of Veillonella parvula strain A- G.I. to modulate antigenspecific CD8+ T cell responses.

[362] Methods: Primary human DCs from 3 healthy donors were differentiated in vitro for 7 days. To assess the immuno-modulatory properties of Veillonella parvula strain A- G.I., DCs were incubated with Veillonella parvula strain A- G.I. for 24 hours in vitro. After 24 hours of microbe conditioning, Veillonella parvula strain A- G.I. was removed from the DC culture and autologous human CD8+ T cells and CEF Class I peptide pool was added. The CEF peptide pool is composed of peptides from Cytomegalovirus, Epstein Bar virus, and Influenza virus, pathogens to which the majority of the human population has been exposed. After 24 hours of stimulation with CEF peptide, DC-CD8+ T cell supernatants were collected and IFNy was measured.

[363] Results: Incubation with Veillonella parvula strain A- G.I. did not inhibit the ability of dendritic cells to induce an IFNy response from CD 8 T cells to CEF viral peptides (neither enhanced nor decreased) compared to the DC-CD8 T cell co-culture control (FIG. 24). These data demonstrate that Veillonella parvula strain A- G.I. does not impair the CD8+ T cell response to viral antigens.

[364] Conclusion

[365] The combination of in vitro, in vivo, and ex vivo data demonstrate that Veillonella parvula strain A- G.I. does not impair either innate or adaptive immune responses. Veillonella parvula strain A- G.I. is orally delivered and gut restricted, and therefore its effect is exerted through local interactions with cells of the small intestine, which are then translated from the gut to the periphery to resolve inflammation. Anti-viral responses such as cytotoxic T cell production of interferon-gamma, innate anti-viral production of IFNa and IFNp, and the generation of high affinity antibodies are all preserved after treatment with Veillonella parvula strain A- G.I.

[366] The data demonstrate that treatment with Veillonella parvula strain A- G.I. results in resolution of multiple pathways of inflammation without leading to overt immunosuppression of the host response. COVID-19-related complications such as hypoxia have been shown to be related to excess inflammation associated with the immune response to the virus. Therefore, Veillonella parvula strain A- G.I. may also theoretically lead to improvement in outcomes in COVID- 19 patients, by reducing this inflammation excess without impairing the host immune response.

Example 7: Powder Preparation Sample Protocol

[367] After desired level of bacterial culture growth is achieved, centrifuge cultures, discard the supernatant, leaving the pellet as dry as possible. Resuspend pellet in desired cryoprotectant solution to create a formulated cell paste. The cryoprotectant may contain, e.g., maltodextrin, sodium ascorbate, sodium glutamate, and/or calcium chloride. Load the formulated cell paste onto stainless steel trays and load into a freeze drier, e.g., operating in automated mode with defined cycle parameters. The freeze-dried product is fed into a milling machine and the resulting powder is collected.

[368] Powders are stored (e.g., in vacuum sealed bags) at 2-8 degrees C (e.g., at 4 degrees C), e.g., in a desiccator.

Example 8: Gamma-Irradiation: Sample Protocol:

[369] Powders are gamma-irradiated at 17.5 kGy radiation unit at ambient temperature. Frozen biomasses are gamma-irradiated at 25 kGy radiation unit in the presence of dry ice.

Example 9: Capsules Comprising revote/fa histicola

[370] Capsules according to the following recipe in Table i were prepared:

Table i: Prevotella histicola Capsule Composition b Adjusted based on the potency of drug substance to ensure targeted strength.

[371] The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329). The capsule was banded with an HPMC -based banding solution. The banded capsule was enteric coated with a poly(methacrylic acid-co-ethyl acrylate) copolymer.

Example 10: Capsule Comprising Prevotella histicola

[372] Capsules according to the following recipe in Table ii were prepared:

Table ii: Prevotella histicola Capsule Composition a Swedish orange Vcap capsules

[373] The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).

[374] The capsule was banded with an HPMC-based banding solution.

[375] The banded capsule was enteric coated with Eudragit L30-D55, a poly(methacrylic acid-co-ethyl acrylate) copolymer.

Example 11: Tablet Comprising Prevotella histicola

[376] As another example, the following recipe in Table iii is prepared.

Table iii: Prevotella histicola Tablet Composition [377] The tablet is prepared as a 17.4mm x 7.1 mm tablet. The tablet is enteric coated. The tablet contains 3.2 x 10 ¹¹ TCC of Prevotella histicola Strain B (NRRL accession number B 50329). The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).

Example 12: Preparation of a capsule comprising Veillonella parvula

[378] Capsules according to the following recipe in Table iv were prepared:

Table iv: Veillonella parvula Capsule Composition

[379] Veillonella parvula has been deposited as Veillonella parvula Strain A (ATCC Deposit Number PTA- 125691).

[380] The Veillonella parvula Strain A bacteria in this capsule were gammairradiated.

[381] The capsule was banded with an HPMC-based banding solution. The banded capsule was enteric coated with a poly(methacrylic acid-co-ethyl acrylate) copolymer.

Example 13: Preparation of a tablet comprising Veillonella parvula

[001] The follow recipe in Table v is prepared: Table v: Compositions of Tablets (400mg)

[002] The Veillonella parvula strain in Table v is Veillonella parvula Strain A

(ATCC Deposit Number PTA- 125691).

[003] The tablet is enteric coated with Kollidon MAE 100P.

Example 14: Inflammation resolution

To examine the effects of Prevotella histicola Strain B on resolving ongoing inflammation: Mice in the ‘post-immunization’ group were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On Day 5 after sensitization, mice were dosed for 4 days with lyophilized Prevotella histicola Strain B powder per os (PO) or dexamethasone (0. 1 mg/kg or 0.4 mg/kg) intraperitoneally (IP). On day 8, baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements.

To examine the effects of pre-dosing Prevotella histicola Strain B on inhibition of inflammation:

Mice in the ‘pre-immunization’ group were dosed for 4 or 8 days with lyophilized Prevotella histicola Strain B powder PO. All mice were then immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On day 8, baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements.

These results (shown in FIG. 25) demonstrate that Prevotella histicola Strain B requires preexisting inflammation to resolve KLH challenge-induced inflammation in the DTH model. If Prevotella histicola Strain B is administered prior to induction of inflammation, the Prevotella histicola Strain B is unable to suppress subsequently induced inflammation in the DTH model.

Example 15: Duration of Effect

Mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On Day 1 after the sensitization, mice were dosed for 8 days with oral Prevotella histicola Strain B (1.82 mg or 10 mg dose; powder form) or dexamethasone (0.1 mg/kg or 0.4 mg/kg) given intraperitoneally. On Day 8, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge. The mice were maintained for two additional weeks. No Prevotella histicola Strain B or dexamethasone were administered during this time. On Day 23, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge.

The results are shown in FIGS. 26A and 26B. After 2 weeks without dosing, dexamethasone efficacy decreased (71% inhibition at Day 8 challenge vs. 55% inhibition at Day 23 challenge) while the effect of Prevotella histicola Strain B on inflammation increased relative to vehicle (32% inhibition at Day 8 challenge vs 48% inhibition at Day 23 challenge for 10 mg dose; 22% inhibition at Day 8 challenge vs 32% inhibition at Day 23 challenge).

These results demonstrate that treatment with Prevotella histicola Strain B leads to a prolonged pharmacodynamic effect, which is maintained in the absence of continuous dosing, as compared to a systemic immuno-suppressive drug such as dexamethasone, which requires continuous dosing to maintain its anti-inflammatory effect. Incorporation by Reference

[382] All publications and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

Equivalents

[383] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.