P1225 The interplay of donor-derived gut microbiota correlates with the efficacy of combination therapy of fecal microbiota transplantation with antibiotics for ulcerative colitis

Abstract

Abstract Background Our previous reports suggest fecal microbiota transplantation (FMT) following bowel cleansing with amoxicillin, fosfomycin, and metronidazole (Antibiotic FMT: A-FMT) improved its efficacy and the recovery of the Bacteroidota species composition, which is associated with ulcerative colitis (UC) severity. Building upon these previous findings, we considered that manipulating the intestinal microbiome to improve the intestinal immune system seems to be a feasible therapeutic regimen for patients with UC. In this study, we explored the gut microbiota signatures through elucidating donor-derived microbe that colonized the recipients and examined the contributions of these microbe to the efficacy of A-FMT. Methods In this study, 97 patients with active UC were enrolled between March 2014 and October 2019, of whom 49 patients were individually assigned a different donor on a one patient-to-one donor basis. FMT was performed via colonoscopy after a two-weeks oral administration of three antibacterial agents. The Lichtiger’s clinical activity index (CAI) at 4 weeks after A-FMT treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points. Each case contributed three fecal samples (pre A-FMT, post A-FMT, and Donor). 16S rRNA gene sequence analysis was performed on 147 collected fecal samples, and 6,501 Amplicon Sequence Variants (ASV) were identified and characterized. Results In responders, the relative abundance of 6 taxonomies including Alistipes were significantly abundant in both post A-FMT treatment samples and their donors’ samples, while 6 other taxonomies were significantly low. In non-responder, significantly low proportion of donor-derived and significantly high proportions of patients-origin and/or new ASV were observed compared with responders. The similarity of gut microbiota composition between donor and post A-FMT treatment was predominantly higher in responders compared to non-responders (Figure 1). Conclusion This study revealed that the engraftment of specific donor-derived microbes is a major factor in A-FMT outcomes, which may be the foundation for precision FMT. Rational identification of patient and donor characteristics can further advance the development of A-FMT therapy for UC.