Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis

Background & Aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition. Methods: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with JBI tools and a composite critical appraisal score. Additionally, species-level data from 2 landmark FMT trials (the Transplantation of Feces in Ulcerative Colitis; Returning Nature's Homeostasis [TURN] and Fecal Microbiota Transplantation for Chronic Active Ulcerative Colitis [FOCUS] trials) were reanalyzed from a compositional perspective. Results: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors’ microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate-producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria, and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides-dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high-diversity composition with abundant but not excessive levels of Prevotella copri. Conclusions: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.