Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis

Abstract

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy. METHODS:We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n ¼ 55), who in turn contributed to 21 multidonor batches (n ¼ 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features. RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Gastroenterology 2019;156:1440-1454 BASIC AND TRANSLATIONAL ATBacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT. CONCLUSIONS:In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

“…Unlike the effect of microflora transplantation on recurrent CDI, the results of many studies on FMT in UC are heterogeneous [123][124][125][126][127][128][129][130][131][132] owing to the lack of a standardized process ( Table 2). 9 One study suggests that the microbial imbalance of the CDI + UC recipients is similar to that of CDI-only recipients 140 Thus, the efficacy for FMT treatment in UC is probably attributed to the occurrence of bacterial dysregulation similar to that seen in CDI.…”

Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies

“…FMT has been shown to result in increased secretory IgA and mucin as well as anti-microbial peptide production, affecting pathogen invasion by antigen/pathogendependent and -independent targeting [65]. In the case of UC, a few randomised controlled trials are currently underway, with one recent study showing that some UC patients could achieve remission following continuous FMT thanks to the observed greater microbial diversity and enrichment of Eubacterium hallii and Roseburia inulivorans in faecal and colon samples [66]. Significantly, the immunological outcomes of FMT are hard to dissect.…”

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

“…This is accompanied by an increased in the biosynthesis of second bile acids and shortchain fatty acids. 166…”