The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis

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.

Predictive Metagenomic Analysis of Autoimmune Disease Identifies Robust Autoimmunity and Disease Specific Microbial Signatures

“…We were able to recapitulate major findings from all studies. For example, we identified disease-specific alterations in multiple studies in Akkermansia 39,31 24,40,39,33,20 and Streptococcus 34 (Fig. 2).…”

“…Following quality control (QC) and filtering, 20 16S rRNA studies remained for downstream analysis (Fig. 1) 19,20,[22][23][24][26][27][28]30,31,[33][34][35][36][37][38][39][40]46,47 . Notably, 8 out of the 20 studies used investigated the role of the human gut microbiome in IBD, due in part to its relatively high prevalence in 1.3% of US adults 48 .…”

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

“…The more abundant the donor microflora are, or to some certain bacteria are, the greater the symptom alleviation via FMT in patients with UC. Targeted therapy through specifically designed microbial agents may be a new approach to the treatment of UC . Brace et al analyzed microbial composition in patients with UC and CDI after treatment with multiple FMT and found that the degree of symptom relief was related to the patient's recovery because of the donor microbiota.…”

“…Targeted therapy through specifically designed microbial agents may be a new approach to the treatment of UC. 148 Brace et al 149…”

Dysbiosis in Functional Bowel Disorders

“…Another potential application is pouchitis [89, 90]. During these studies, a number of mediators of treatment success were identified, among them the donor, the route of administration of the stool transplant, and others [91, 92]. …”