Faculty Collaboration Database

Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients. Sci Rep 2024 Aug 09;14(1):18558

Date

08/10/2024

Pubmed ID

39122767

Pubmed Central ID

PMC11316000

DOI

10.1038/s41598-024-62463-8

Scopus ID

2-s2.0-85200883202 (requires institutional sign-in at Scopus site)   6 Citations

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.

Author List

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, Lynch SV

Author

Test W. User test user title in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Bacteroides
Colitis, Ulcerative
Fecal Microbiota Transplantation
Feces
Female
Gastrointestinal Microbiome
Humans
Intestinal Mucosa
Male
Metabolome
Middle Aged
RNA, Ribosomal, 16S
Treatment Failure