Abstract

Abstract Background Evidence continues to accumulate highlighting the potential of fecal microbiota transplantation (FMT) to induce remission in patients with ulcerative colitis (UC). However, rational donor and recipient selection strategies and predictive biomarkers are needed to increase its efficacy. This systematic review provides a comprehensive evaluation of the current literature on microbial factors of FMT donors and UC recipients that relate to clinical outcomes. Methods The MEDLINE, Embase and Cochrane databases were systematically searched through April 2023 for relevant studies. The quality of studies and risk of bias was analyzed with Joanna Briggs tools and a compound critical appraisal-score. Additionally, species-level data from two randomized controlled trials (TURN and FOCUS) were re-analyzed from a compositional perspective. Results Out of 2983 citations identified, 47 met the inclusion criteria, of which 20 fulfilled quality appraisal. Higher clinical response rates were associated with higher bacterial alpha-diversity of stools of UC recipients at baseline and following FMT, and with higher FMT donor alpha-diversity. Engraftment of the donors’ microbiota was often reported but could not be clearly linked to clinical response, possibly because not every donor has an ideal microbiome. Taxa most frequently reported to be related to response included members of the Lachnospiraceae family (e.g., Eubacterium rectale, Blautia obeum) and Oscillospiraceae family (e.g., Faecalibacterium prausnitzii, Ruminococcus bromii) whereas members of the Proteobacteria and Fusobacteria phyla and Ruminococcus gnavus were reported to correlate to non-response. Low virome richness and low Caudovirales bacteriophages at baseline as well as a decrease of Candida levels following FMT, were associated with clinical response. Compositional analyses showed that a clinical response is associated with a shift away from a low diversity, Bacteroides2-enterotype-like composition towards one of high diversity either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network or a high diversity composition with abundant but not excessive levels of Prevotella copri. Conclusion In this systematic review we found distinctive features of microbial profiles of both donors and UC recipients to relate to clinical response to FMT. The predictive value of microbial markers should be further explored in future clinical studies to move towards a personalized FMT approach and delineate ‘super-donor’ profiles.

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