Network-based microbial compositions and methods
Provided are therapeutic compositions containing combinations of bacteria, for the maintenance or restoration of a healthy microbiota in the gastrointestinal tract of a mammalian subject, and methods for use thereof.
1. A composition comprising a plurality of isolated bacteria and a capsule which encapsulates the plurality of isolated bacteria, wherein the plurality of isolated bacteria comprises a first bacterial operational taxonomic unit (OTU) comprising a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 774, a second bacterial OTU comprising a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 856, a third bacterial OTU comprising a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 880, and a fourth bacterial OTU comprising a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 1670.
2. The composition of claim 1 , wherein the first bacterial OTU comprises a 16S rDNA sequence that is at least 98% identical to SEQ ID NO: 774, the second bacterial OTU comprises a 16S rDNA sequence that is at least 98% identical to SEQ ID NO: 856, the third bacterial OTU comprises a 16S rDNA sequence that is at least 98% identical to SEQ ID NO: 880, and the fourth bacterial OTU comprises a 16S rDNA sequence that is at least 98% identical to SEQ ID NO: 1670.
3. The composition of claim 1 , wherein the first bacterial OTU comprises a 16S rDNA sequence that is at least 99% identical to SEQ ID NO: 774, the second bacterial OTU comprises a 16S rDNA sequence that is at least 99% identical to SEQ ID NO: 856, the third bacterial OTU comprises a 16S rDNA sequence that is at least 99% identical to SEQ ID NO: 880, and the fourth bacterial OTU comprises a 16S rDNA sequence that is at least 99% identical to SEQ ID NO: 1670.
4. The composition of claim 1 , wherein the first bacterial OTU comprises the 16S rDNA sequence set forth in SEQ ID NO: 774, the second bacterial OTU comprises the 16S rDNA sequence set forth in SEQ ID NO: 856, the third bacterial OTU comprises the 16S rDNA sequence set forth in SEQ ID NO: 880, and the fourth bacterial OTU comprises the 16S rDNA sequence set forth in SEQ ID NO: 1670.
5. The composition of claim 1 , wherein the first bacterial OTU is Dorea longicatena , the second bacterial OTU is Eubacterium rectale , the third bacterial OTU is Faecalibacterium prausnitzii , and the fourth bacterial OTU is Ruminococcus torques.
6. The composition of claim 1 , which is substantially depleted of (i) a pathogenic material, (ii) a residual habitat product of a fecal material, or (iii) both.
7. The composition of claim 1 , wherein one or more bacteria of the plurality of isolated bacteria are in a spore form.
8. The composition of claim 1 , wherein one or more bacteria of the plurality of isolated bacteria are in a vegetative form.
9. The composition of claim 1 , wherein one or more bacteria of the plurality of isolated bacteria are lyophilized.
10. The composition of claim 1 , which further comprises one or more anti-microbial agents.
11. The composition of claim 10 , wherein the one or more anti-microbial agents are selected from an anti-bacterial agent, an anti-fungal agent, an anti-viral agent, an anti-parasitic agent, or any combination thereof.
12. The composition of claim 1 , which is capable of inducing the formation of IgA, RegIII-gamma, IL-10, regulatory T cells, TGF-beta, alpha-defensin, beta-defensin, or any combination thereof when administered to a mammalian subject.
13. The composition of claim 1 , which is prepared by an ethanol treatment.
14. The composition of claim 1 , which is prepared by a heat treatment.
15. A single dosage unit comprising the composition of claim 1 .
16. A pharmaceutical formulation comprising the composition of claim 1 and an excipient.
17. The pharmaceutical formulation of claim 16 , which is formulated for oral administration.
18. The composition of claim 1 , which further comprises glycerol.
19. The composition of claim 7 , wherein the plurality of isolated bacteria are in a spore form.
20. The composition of claim 19 , which comprises between about 1×10 6 to about 1×10 15 colony forming units (CFUs) of the plurality of isolated bacteria.
21. A pharmaceutical formulation comprising the composition of claim 19 and an excipient.
22. A pharmaceutical formulation comprising the composition of claim 20 and an excipient.