P136 Immunomodulatory mechanisms of FMT is associated with clinical response in UC – results from STOP-Colitis

Background Studies of faecal microbiota transplantation (FMT) for treating ulcerative (UC) have shown promising results, however mechanisms by which FMT modulates inflammation remain unexplored. Through an 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 8 infusions of FMT over an 8 week period. Colon biopsies were obtained at baseline and at end of the study. Immunophenotyping of colonic lamina propria mononuclear cells (LPMC) and RNA sequencing was conducted on colon biopsies for differential gene expression analysis. Results 17 patients were recruited to this sub-study of which 12 completed study 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+; Δ5.02%; p 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. Exploring microbial mediators in FMT which influence immunometabolism are now under investigation to underpin novel biotherapeutic approaches.