Novel Microbial Engraftment Trajectories Following Microbiota Transplant Therapy in Ulcerative Colitis

Abstract

Background and aims: Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC. Methods: Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker. Results: Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose. Conclusion: SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.