Compositions comprising bacterial strains
The invention provides compositions comprising bacterial strains for stimulating the immune system and treating and preventing diseases.
1. A method of increasing differentiation of cytotoxic T cells in a subject in need thereof, comprising
administering to the subject a pharmaceutical composition that comprises a bacteria strain of the genus Enterococcus , wherein the bacteria strain comprises a 16S rRNA gene sequence that has at least 95% sequence identity to the polynucleotide sequence of SEQ ID NO: 2, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2,
wherein the subject has been diagnosed with deficient immune activity, and
wherein the administering is sufficient to increase differentiation of cytotoxic T cells in the subject, relative to a level of differentiation of cytotoxic T cells in the subject prior to the administering.
2. The method of claim 1 , wherein the cytotoxic T cells are CD8 cells, and wherein the administering is sufficient to increase a level of CD8 cells in a serum of the subject, relative to a level of CD8 cells in the serum of the subject prior to the administering.
3. The method of claim 1 , wherein the administering increases differentiation of T helper cells, relative to a level of differentiation of T helper cells in the subject prior to the administering.
4. The method of claim 1 , wherein the administering activates a toll-like receptor (TLR) signaling pathway in the subject.
5. The method of claim 4 , wherein the TLR is TLR5 or TLR9.
6. The method of claim 1 , wherein the administering increases a level of a cytokine in a serum of the subject, relative to a level of the cytokine in the serum of the subject prior to the administering.
7. The method of claim 6 , wherein the cytokine is IL-6 or IL-23.
8. The method of claim 1 , wherein the administering increases a level of NFκBIA in the subject, relative to a level of NFκBIA in the subject prior to the administering.
9. The method of claim 1 , wherein the administering comprises oral, rectal, nasal, buccal, sublingual, or subcutaneous administration.
10. The method of claim 1 , wherein the bacterial strain is dried.
11. The method of claim 1 , wherein the pharmaceutical composition comprises from about 1×10 3 to about 1×10 11 colony forming units (CFU)/g of the bacteria strain with respect to the total weight of the pharmaceutical composition.
12. The method of claim 1 , wherein the bacteria strain at least partially colonizes an intestine of the subject.
13. The method of claim 1 , wherein the pharmaceutical composition is formulated for delivery to an intestine of the subject.
14. The method of claim 1 , wherein the bacteria strain comprises a 16S rRNA gene sequence that has at least 99% sequence identity to the polynucleotide sequence of SEQ ID NO: 2, as determined by a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2.
15. The method of claim 1 , wherein the bacteria strain comprises a 16S rRNA gene sequence that is the polynucleotide sequence of SEQ ID NO: 2 or SEQ ID NO: 3.
16. The method of claim 1 , wherein the bacterial strain is of the species Enterococcus gallinarum.
17. The method of claim 1 , wherein the bacterial strain is the strain deposited under accession number NCIMB 42488 or the strain deposited under accession number NCIMB 42761.
18. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients, carriers, or diluents.
19. The method of claim 1 , further comprising administering a cell therapy to the subject.
20. The method of claim 19 , the cell therapy is chimeric antigen receptor T cell (CAR-T) therapy, mesenchymal stem cell (MSC) therapy, stem cell transplantation therapy, or hematopoietic stem cell transplantation.