Novel Microbial Engraftment Trajectories following Microbiota Transplantation Therapy in Ulcerative Colitis.

Abstract

Background and aims: Microbiota transplant therapy is an emerging treatment for ulcerative colitis. One proposed mechanism for the benefit of microbiota transplant therapy is through engraftment of donor microbiota. However, the kinetics of engraftment 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 ulcerative colitis.

Methods: Ulcerative colitis patients were treated with either encapsulated (drug name MTP-101C) or placebo capsules daily for eight weeks followed by a four-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 the placebo group and 13 to the microbiota transplant therapy group. 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. We identified engrafting taxa from donors in our patients as well as quantified the proportion of donor similarity or engraftment during weeks one through eight (active treatment) and week 12, four 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 ulcerative colitis and other inflammatory conditions treated with microbiota transplant therapy.