Donor Gut MicrobialDrives Fecal Microbiota Transplantation Efficacy in ulcerative colitis

Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic strategy for Inflammatory Bowel Disease (UC), though its clinical success appears contingent upon donor microbiota engraftment degree. While microbial colonization dynamics remain poorly understood, our study identifies metabolism as a critical determinant of gut community assembly under UC nutrient-limiting intestinal conditions. Using an model, we demonstrate that microbial competence in influences engraftment outcomes. Building on this mechanistic insight, we engineered a novel probiotic-metabolite consortium (G-MIX) designed to synergistically enhance gut ecosystems. Through multi-step catalytic conversion G-MIX facilitates L-glutamate biosynthesis and ATP generation, thereby alleviating RNS-mediated barriers to donor microbiota colonization. In murine UC models, G-MIX supplementation during FMT significantly improved microbial engraftment fidelity, correlating with enhanced anti-inflammatory responses and attenuated colonic pathology. Network meta-analysis of clinical datasets further substantiated the prognostic value of donorin UC remission. Our findings utilisation as an ecological driver of microbiota engraftment and present a rationally designed microbial therapy that optimises FMT efficacy through targeted metabolic reprogramming.