Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial

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

doi:10.1093/ecco-jcc/jjag006

Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial

Mohammed Nabil Quraishi (Lead / Corresponding author)
, 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 (Lead / Corresponding author)

Respiratory Medicine and Gastroenterology

Research output: Contribution to journal › Article › peer-review

4 Downloads (Pure)

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.

Original language	English
Article number	jjag006
Number of pages	12
Journal	Journal of Crohn's and Colitis
Volume	20
Issue number	3
Early online date	23 Jan 2026
DOIs	https://doi.org/10.1093/ecco-jcc/jjag006
Publication status	Published - 24 Mar 2026

Keywords

fecal microbiota transplantation
ulcerative colitis
immunology

Access to Document

10.1093/ecco-jcc/jjag006Licence: CC BY

Final Published VersionFinal published version, 3.41 MBLicence: CC BY

Cite this

Quraishi, M. N., Moakes, C. A., Yalchin, M., Blackwell, C., Segal, J., Ives, N. J., Magill, L., Manzoor, S. E., Gerasimidis, K., McMullan, C., Mathers, J., Horniblow, R., Loi, S., Kaur, M., Loman, N. J., Sharma, N., Hawkey, P., McCune, V., Quick, J., ... Iqbal, T. H. (2026). Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial. Journal of Crohn's and Colitis, 20(3), Article jjag006. https://doi.org/10.1093/ecco-jcc/jjag006

@article{099e4e12e52546c3b2fe98de23835f10,

title = "Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial",

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.",

keywords = "fecal microbiota transplantation, ulcerative colitis, immunology",

author = "Quraishi, \{Mohammed Nabil\} and Moakes, \{Catherine A.\} and Mehmet Yalchin and Claire Blackwell and Jonathan Segal and Ives, \{Natalie J.\} and Laura Magill and Manzoor, \{Susan E.\} and Konstantinos Gerasimidis and Christel McMullan and Jonathan Mathers and Richard Horniblow and Shrushma Loi and Manjinder Kaur and Loman, \{Nicholas J.\} and Naveen Sharma and Peter Hawkey and Victoria McCune and Joshua Quick and Samuel Nicholls and Claire McMurray and Ben Nichols and Vaios Svolos and Sebastien Raguideau and Caroline Kerbiriou and Oo, \{Ye H.\} and Beggs, \{Andrew D.\} and Nicola Crees and Richard Hansen and Hart, \{Ailsa L.\} and Gaya, \{Daniel R.\} and Christopher Quince and Iqbal, \{Tariq H.\}",

note = "Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of European Crohn{\textquoteright}s and Colitis Organisation.",

year = "2026",

month = mar,

day = "24",

doi = "10.1093/ecco-jcc/jjag006",

language = "English",

volume = "20",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Oxford University Press",

number = "3",

}

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 2026, 'Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial', Journal of Crohn's and Colitis, vol. 20, no. 3, jjag006. https://doi.org/10.1093/ecco-jcc/jjag006

TY - JOUR

T1 - Mechanistic insights into FMT for the treatment of ulcerative colitis

T2 - analysis of the STOP-Colitis trial

AU - Quraishi, Mohammed Nabil

AU - Moakes, Catherine A.

AU - Yalchin, Mehmet

AU - Blackwell, Claire

AU - Segal, Jonathan

AU - Ives, Natalie J.

AU - Magill, Laura

AU - Manzoor, Susan E.

AU - Gerasimidis, Konstantinos

AU - McMullan, Christel

AU - Mathers, Jonathan

AU - Horniblow, Richard

AU - Loi, Shrushma

AU - Kaur, Manjinder

AU - Loman, Nicholas J.

AU - Sharma, Naveen

AU - Hawkey, Peter

AU - McCune, Victoria

AU - Quick, Joshua

AU - Nicholls, Samuel

AU - McMurray, Claire

AU - Nichols, Ben

AU - Svolos, Vaios

AU - Raguideau, Sebastien

AU - Kerbiriou, Caroline

AU - Oo, Ye H.

AU - Beggs, Andrew D.

AU - Crees, Nicola

AU - Hansen, Richard

AU - Hart, Ailsa L.

AU - Gaya, Daniel R.

AU - Quince, Christopher

AU - Iqbal, Tariq H.

PY - 2026/3/24

Y1 - 2026/3/24

N2 - 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.

AB - 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.

KW - fecal microbiota transplantation

KW - ulcerative colitis

KW - immunology

U2 - 10.1093/ecco-jcc/jjag006

DO - 10.1093/ecco-jcc/jjag006

M3 - Article

C2 - 41587946

SN - 1873-9946

VL - 20

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 3

M1 - jjag006

ER -

Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial

Abstract

Keywords

Access to Document

Fingerprint

Cite this