Presented by: Varun Aggarwala
Several placebo-controlled trials have demonstrated that FMT can induce remission in a subset of patients (27-53% response rate) with Ulcerative Colitis (UC). However open questions regarding FMT study design, dosage, choice of donors, strain level dynamics and predictors of response remain unanswered. Here, we comprehensively culture 551 bacterial isolates from 13 donors in the successful FMT FOCUS trial for UC patients, and tracked their engraftment and inter-intra strain dynamics (each patient received FMT from 4-7 donors) in 243 longitudinal metagenomics samples upto 5 years later from 55 recipients. We detect high and stable engraftment (p value < 0.001) of donor strains in patients achieving the primary endpoint of corticosteroid-free clinical remission together with endoscopic remission or response at week 8 compared to those that did not. This reduced at year 5 (coinciding with relapse) and reaches the level (p value < 0.01) seen in patients who had not achieved the endpoint earlier. Patients who only received 40 doses of enema (open phase) did not have lower engraftment or response compared to patients who also received an added initial colonoscopic infusion (blind phase). 40 doses of enema at week 8 did not result in higher engraftment compared to receiving 20 by week 4. High engraftment from individual donors increased the odds for achieving the endpoint (p value < 0.05) and the most effective donor in FOCUS trial was also found to have 100% efficacy (n=4) in another FMT LOTUS trial for UC patients. We provide a list of bacterial strains that are over-enriched and stably engrafted in recipients achieving the endpoint compared to those that did not, and for use in Live Biotherapeutic Products (LBP) as a safer alternative to FMT.