OP09 Immunomodulatory mechanisms of faecal microbiota transplantation are associated with clinical response in ulcerative colitis: early results from STOP-Colitis
M.N. Quraishi1,2, Y.H. Oo3, A. Beggs4, D. Withers3, A. Acharjee4,5, N. Sharma1,2, S. Manzoor1, A.L. Hart6, D.R. Gaya7, N.J. Loman8, P.M. Hawkey1, K. Gerasimidis9, R. Hansen10, G. Gkoutous4,5,11, T.H. Iqbal1,2
1University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, UK, 2Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, 3Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK, 4Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK, 5NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK, 6IBD Unit, St Marks Hospital, London, UK, 7Gastroenterology Unit, Glasgow Royal Infirmary, Glasgow, UK, 8Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK, 9Human Nutrition- School of Medicine- Dentistry and Nursing, University of Glasgow, Glasgow, UK, 10Department of Paediatric Gastroenterology, Royal Hospital for Children Glasgow, Glasgow, UK, 11MRC, Health Data Research UK, Birmingham, UK
Background
Studies of faecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. Mechanisms by which FMT modulates inflammation, however, remain unexplored. Through a prospective, open-label pilot of FMT in UC (STOP-Colitis) we conducted a sub-study to explore changes in host colonic mucosal immune cell subsets and gene expression following FMT.
Methods
Patients in this study received eight infusions of FMT over an 8-week period. Colon biopsies and blood were obtained at baseline and at the end of the study. Immunophenotyping of colonic lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) was conducted. RNA sequencing was performed on colon biopsies for differential gene expression analysis followed by multi-omic integration.
Results
Seventeen patients were recruited to this sub-study; of which, 12 completed 8 weeks of FMT per protocol. Response (reduction in MAYO score) was seen in 67% (8/12) of patients. Analysis of colonic LPMC populations revealed a significant increase in regulatory T cells (Tregs, CD4+CD25+CD127lowFoxP3+; Δ 5.02%;
Conclusion
Response to FMT is associated with a significant increase in mucosal gut homing Tregs and butanoate metabolism along with a reduction in Th17 cells and multiple anti-microbial defence and proinflammatory pathways. FMT induces change in immune balance in local milieu which leads to clinical response in UC. Exploring microbial mediators in FMT which influence immunometabolism is now under investigation to underpin novel biotherapeutic approaches.