Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients
Recommended Citation
Zhang B, Magnaye KM, Stryker E, Moltzau-Anderson J, Porsche CE, Hertz S, McCauley KE, Smith BJ, Zydek M, Pollard KS, Ma A, El-Nachef N, and Lynch SV. Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients. Sci Rep 2024; 14(1):18558.
Document Type
Article
Publication Date
8-9-2024
Publication Title
Sci Rep
Abstract
Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.
Medical Subject Headings
Humans; Colitis, Ulcerative; Fecal Microbiota Transplantation; Male; Female; Feces; Bacteroides; Adult; Intestinal Mucosa; Middle Aged; Gastrointestinal Microbiome; Treatment Failure; RNA, Ribosomal, 16S; Metabolome
PubMed ID
39122767
Volume
14
Issue
1
First Page
18558
Last Page
18558
