Methods and compositions for treating ulcerative colitis
The present disclosure provides methods and pharmaceutical compositions for treating ulcerative colitis (UC) in a subject in need thereof. In particular, the compositions described here comprise or are designed based on fecal bacteria associated with FMT-based UC treatment success or failure. Also provided are methods for screening patients for their suitability for a fecal bacteria-based UC treatment. Further provided are methods for screening fecal donors for optimized source materials for producing a fecal bacteria-based pharmaceutical composition.
1. A method of manufacturing a fecal microbe preparation comprising a bacterial strain for incorporation into a pharmaceutical composition, the method comprising:
a) selecting a source material from a human donor based on a higher relative abundance of a metabolite in the source material, wherein the metabolite is selected from the group consisting of a secondary bile acid, a short chain fatty acid (SCFA), and a combination thereof, wherein the human donor is a member of a plurality of donors, and the higher relative abundance is relative to the average relative abundance of the metabolite in source material of the plurality of donors; and
b) harvesting the bacterial strain from the selected source material to produce the fecal microbe preparation.
2. The method of claim 1 , wherein the pharmaceutical composition is formulated so as to be suitable for treating ulcerative colitis (UC).
3. The method of claim 1 , wherein the metabolite is the secondary bile acid.
4. The method of claim 1 , wherein a plurality of samples of source material from the human donor are selected.
5. The method of claim 1 , wherein the harvesting comprises culturing the bacterial strain.
6. The method of claim 5 , wherein the cultured bacterial strain is from a genus selected from the group consisting of Eubacterium, Bacteroides, Faecalibacterium and Roseburia.
7. The method of claim 6 , wherein the genus is Eubacterium and the bacterial species is Eubacterium rectale.
8. The method of claim 6 , wherein the genus is Faecalibacterium and the bacterial species is Faecalibacterium prausnitzii.
9. The method of claim 5 , wherein the method further comprises supplementing the fecal microbe preparation with viable cultured bacteria.
10. The method of claim 9 , wherein the viable cultured bacteria comprise lyophilized bacteria.
11. The method of claim 1 , wherein the pharmaceutical composition comprises a capsule, and the method further comprises incorporating the fecal microbe preparation into the capsule.
12. The method of claim 1 , wherein the metabolite is a SCFA.
13. The method of claim 12 , wherein the SCFA is butyrate.
14. The method of claim 1 , wherein the metabolite comprises both the SCFA and the secondary bile acid.
15. The method of claim 1 , further comprising lyophilizing the fecal microbe preparation in the presence of a cryoprotectant.
16. The method of claim 1 , further comprising spray-drying the fecal microbe preparation.
17. The method of claim 15 , wherein the cryoprotectant is selected from the group consisting of polyethylene glycol, skim milk, erythritol, arabitol, sorbitol, glucose, fructose, alanine, glycine, proline, sucrose, lactose, ribose, trehalose, dimethyl sulfoxide (DMSO), glycerol, or a combination thereof.
18. The method of claim 17 , wherein the cryoprotectant is trehalose.
19. The method of claim 1 , wherein the fecal microbe preparation comprises a community of microbes harvested from the source material.
20. The method of claim 3 , wherein the secondary bile acid is selected from the group consisting of lithocholic acid, deoxycholic acid, ursodeoxycholic acid, and a combination thereof.