Abstract
SummaryBackgroundFaecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.AimsTo establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.MethodsThis is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre‐treatment (FMT‐group, n = 17) vs antibiotic pre‐treatment only (AB‐group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene‐based microbiota analysis.ResultsIn the FMT‐group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB‐group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.ConclusionsThe taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.
Highlights
Ulcerative colitis is an inflammatory bowel disease of the colon of unknown aetiology
One hypothesis of ulcerative colitis pathogenesis suggests that changes in the composition of colonic microbiota, called dysbiosis, cause activation of the mucosal immune system resulting in chronic inflammation.[1,2,3,4]
As dysbiosis is believed to be a significant player in the pathogenesis of ulcerative colitis, the use of faecal microbiota transplantation has been studied in various case series[12,13,14,15,16,17,18] and in four small randomised controlled trials.[19,20,21,22]
Summary
Ulcerative colitis is an inflammatory bowel disease of the colon of unknown aetiology. In a recent systematic review of studies, an average response rate of 49%-55% and remission rate of 24%-28% was reported.[17] Three of the controlled trials[20,21,22] showed a superiority of faecal microbiota transplantation compared to placebo while one trial failed[19] to demonstrate a difference between faecal microbiota transplantation and the control group. It remains unclear why some patients respond to this form of therapy while others do not. The large variability of faecal microbiota transplantation efficacy in ulcerative colitis patients raised several questions regarding the right faecal microbiota transplantation protocol or patient factors influencing treatment success.[17]
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