Compositions comprising bacterial strains
The invention provides compositions comprising bacterial strains for treating and preventing inflammatory and autoimmune diseases.
1. A pharmaceutical composition that reduces inflammation associated with Th17 differentiation in a subject in need thereof, that comprises a therapeutically effective amount of a single bacteria strain of the species Erysipelatoclostridium ramosum ; and
a pharmaceutically acceptable excipient, diluent, or carrier;
wherein the therapeutically effective amount comprises from about 1×10 3 to about 1×10 11 CFU of the bacteria strain;
wherein the bacterial strain is lyophilized; and
wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO:3, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a Blocks Substitution Matrix (BLOSUM) of 62.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient or carrier comprises a lyoprotectant.
3. The pharmaceutical composition of claim 1 , wherein the bacteria strain comprises the polynucleotide sequence of SEQ ID NO:3.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition consists essentially of the bacteria strain of species Erysipelatoclostridium ramosum.
5. The pharmaceutical composition of claim 1 , further comprising at least one additional bacteria strain.
6. The pharmaceutical composition of claim 1 , wherein at least 50% of the bacteria strain as measured by an amount of colony forming units (CFU) remains viable after about 1 year of storage when the pharmaceutical composition is stored in a closed container at 25° C. at 95% relative humidity.
7. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount comprises from about 1×10 6 to about 1×10 11 CFU/g of the bacteria strain with respect to a total weight of the pharmaceutical composition.
8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral delivery, and wherein the pharmaceutical composition comprises an enteric coating.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a prebiotic compound selected from the group consisting of: a fructo-oligosaccharide, a short-chain fructo-oligosaccharide, inulin, an isomalt-oligosaccharide, a transgalacto-oligosaccharide, a pectin, a xylo-oligosaccharide, a chitosan-oligosaccharide, a beta-glucan, an arable gum modified starch, a polydextrose, a D-tagatose, an acacia fiber, carob, an oat, and a citrus fiber.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises an adjuvant.
11. A method of treating a condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition that comprises a bacteria strain of the species Erysipelatoclostridium ramosum and a pharmaceutically acceptable excipient, diluent, or carrier;
wherein the bacteria strain is present in an amount sufficient for treating a condition mediated by the Th17 pathway or by an increase in the IL-17 cytokine in the subject;
wherein the therapeutically effective amount comprises from about 1×10 3 to about 1×10 11 CFU of the bacteria strain;
wherein the bacteria strain is lyophilized; and
wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 95% identity to the polynucleotide sequence of SEQ ID NO:3, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a Blocks Substitution Matrix (BLOSUM) of 62.
12. The method of claim 11 , wherein the condition mediated by the Th17 pathway or by an increase in the IL-17 cytokine is uveitis, and wherein said treating or preventing comprises reducing or preventing retinal damage in uveitis.
13. The method of claim 11 , wherein the bacteria strain is present in an amount sufficient for treating the condition mediated by the Th17 pathway, wherein the condition mediated by the Th17 pathway is a cancer, and wherein the cancer is breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer.
14. The method of claim 11 , wherein the bacteria strain comprises the polynucleotide sequence of SEQ ID NO:3.
15. The method of claim 11 , wherein the subject has the condition, or has been identified as being at risk of the condition.
16. The method of claim 11 , further comprising administering an additional therapeutic agent to the subject.
17. The method of claim 11 , wherein the bacteria strain comprises a polynucleotide sequence of a 16s rRNA gene that has at least 99.5% sequence identity to the polynucleotide of SEQ ID NO:3, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12, a gap extension penalty of 2, and a BLOSUM of 62.
18. The method of claim 11 , wherein the bacteria strain is the strain deposited under accession number NCIMB 42688.
19. The pharmaceutical composition of claim 1 , wherein the bacteria strain is the strain deposited under accession number NCIMB 42688.
20. The pharmaceutical composition of claim 1 , wherein the bacteria strain is strain JCM 1298.
21. The pharmaceutical composition of claim 1 , wherein the bacteria has a fermentation profile of a bacteria strain selected from the group consisting of ATCC 25582, JCM 1298, and MRX027.
22. The pharmaceutical composition of claim 1 , wherein the bacteria has a fermentation profile of a bacteria strain deposited under accession number NCIMB 42689.
23. The pharmaceutical composition of claim 1 , wherein the bacteria strain is not in sporulated form or comprises spores in a de minimis amount.