Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial
Quraishi, Mohammed Nabil Moakes, Catherine A Yalchin, Mehmet Blackwell, Claire Segal, Jonathan Ives, Natalie J Magill, Laura Manzoor, Susan E Gerasimidis, Konstantinos McMullan, Christel
Quraishi, Mohammed Nabil
Moakes, Catherine A
Yalchin, Mehmet
Blackwell, Claire
Segal, Jonathan
Ives, Natalie J
Magill, Laura
Manzoor, Susan E
Gerasimidis, Konstantinos
McMullan, Christel
Abstract
BACKGROUND AND AIMS: Faecal microbiota transplantation (FMT) is a promising therapy for ulcerative colitis, but variable responses and unclear mechanisms limit its efficacy. We aimed to compare nasogastric versus colonic FMT delivery and define the microbial and immunological changes associated with clinical response.
METHODS: In this prospective, open-label, randomised pilot trial (STOP-Colitis), 30 adults with active ulcerative colitis were randomised to receive multi-dose FMT via nasogastric tube or colonoscopy with subsequent enemas. Key endpoints were clinical outcomes at week 8 and longitudinal multi-omic analyses of stool and biopsies to define changes in microbial composition (16S rRNA and shotgun metagenomics), short-chain fatty acids, mucosal T-cells, and host gene expression.
RESULTS: Colonic FMT was superior to nasogastric delivery, with a higher clinical response rate at week 8 (75% [9/12] vs 25% [2/8]; RR 2·94, 95% CI 0·84-10·30-per protocol analysis). Response was underpinned by successful microbial engraftment, leading to significantly increased faecal microbial diversity and enrichment of SCFA-producing taxa, including Oscillospiraceae and Christensenellaceae. This correlated with reduced faecal calprotectin. Responders showed a significant increase in mucosal regulatory T cells (P = 0·01), with a concurrent decrease in Th17 (P = 0·03) and CD8 + T cells. This anti-inflammatory shift was confirmed by mucosal transcriptomics, which revealed upregulation of metabolic pathways and downregulation of proinflammatory defence pathways in responders. (Trial registration: ISRCTN13636129).
CONCLUSION: Colonic FMT is a more effective delivery route than nasogastric administration. Clinical response is driven by the engraftment of immunomodulatory bacteria that restore a healthy host-microbe dialogue, providing rationale for developing targeted microbial therapeutics.
MIDER Authors
Date
2026-01-23
Type
Article
Subject
faecal microbiota transplantation, immunology, colitis, ulcerative
Collections
Citation
Quraishi MN, Moakes CA, Yalchin M, Blackwell C, Segal J, Ives NJ, Magill L, Manzoor SE, Gerasimidis K, McMullan C, Mathers J, Horniblow R, Loi S, Kaur M, Loman NJ, Sharma N, Hawkey P, McCune V, Quick J, Nicholls S, McMurray C, Nichols B, Svolos V, Raguideau S, Kerbiriou C, Oo YH, Beggs AD, Crees N, Hansen R, Hart AL, Gaya DR, Quince C, Iqbal TH. Mechanistic insights into fecal microbiota transplantation for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial. J Crohns Colitis. 2026 Mar 10;20(3):jjag006. doi: 10.1093/ecco-jcc/jjag006.
Journal / Source Title
Journal of Crohn's & colitis
DOI
10.1093/ecco-jcc/jjag006
PMID
41587946
Publisher
Elsevier Science