Mechanistic insights into fecal microbiota transplantation for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial
Year: 2026
Type: article
Abstract: BACKGROUND AND AIMS: Fecal 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, randomized pilot trial (STOP-Colitis), 30 adults with active ulcerative colitis were randomized to receive multidose 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 (SCFAs), 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]; risk ratio 2.94, 95% CI 0.84-10.30-per protocol analysis). Response was underpinned by successful microbial engraftment, leading to significantly increased fecal microbial diversity and enrichment of SCFA-producing taxa, including Oscillospiraceae and Christensenellaceae. This correlated with reduced fecal calprotectin. Responders showed a significant increase in mucosal regulatory T cells (P = .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 defense pathways in responders. (Trial registration: ISRCTN74072945). 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.
Source: Journal of Crohn s and Colitis
Authors: Mohammed Nabil Quraishi, Catherine A Moakes, Mehmet Yalchin, Claire Blackwell, Jonathan Segal, Natalie J Ives, Laura Magill, Susan E Manzoor, Konstantinos Gerasimidis, Christel McMullan, Jonathan Mathers, Richard Horniblow, Shrushma Loi, Manjinder Kaur, Nicholas J Loman, Naveen Sharma, Peter Hawkey, Victoria McCune, Joshua Quick, Samuel Nicholls, Claire McMurray, Ben Nichols, Vaios Svolos, Sebastien Raguideau, Caroline Kerbiriou, Ye H Oo, Andrew D Beggs, Nicola Crees, Richard Hansen, Ailsa L Hart, Daniel R Gaya, Christopher Quince, Tariq H Iqbal
Institutions: University Hospitals Birmingham NHS Foundation Trust, Sheikh Shakhbout Medical City, University of Birmingham, St Mark's Hospital, Glasgow Royal Infirmary, University of Glasgow, South Tees Hospitals NHS Foundation Trust, Earlham Institute, NIHR Birmingham Biomedical Research Centre, Crohn's and Colitis UK, University of Dundee
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
OpenAlex ID: W7125814875