Development of a Microbial Compounding Pharmacy for Precision Treatment of Ulcerative Colitis Patients.

Fecal Microbial Transplant as a therapeutic modality for ulcerative colitis is effective in approximately 40% of patients. Trials of FMT offer the opportunity to identify the specific microbial functions and strains that promote disease remission and to develop more refined, high potency interventions comprised of groups of microbial strains that increase treatment efficacy. Microbes naturally exist as networks of functionally synergistic organisms whose collective activities modulate host immunity. We propose to identify mucosal-associated microbial functional gene networks encoded by transcriptionally active strains that promote resolution of colonic inflammation in FMT-responsive UC patients. Strains encoding these genes will be identified, isolated, genotyped and phenotyped and used to reconstruct communities of microbes that promote disease remission in human populations. These efforts aim to enable development of a microbial compounding pharmacy from which highly characterized synergistic strain compendiums may be formulated and tested for their capacity to reassemble, become transcriptionally active and promote resolution of colonic inflammation in pre-clinical humanized germ-free mouse models of colitis. Thus, we aim to leverage findings from FMT trials of UC patients to develop functionally defined and quality controlled microbial therapeutics for pre-clinical efficacy testing and ultimately, for tailored treatment of ulcerative colitis.