Abstract
BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for inflammatory bowel disease (IBD), achieving clinical response rate of ~50% for ulcerative colitis (UC), and Crohn's disease (CD). While prior research has emphasized donor selection and treatment protocols, the role of the patient's native intestinal microbiota in FMT outcomes remains underexplored. METHODS: This study analyzed a retrospective cohort of 96 IBD patients (45 CD, 51 UC) undergoing FMT, with 192 paired stool samples collected pre- and post-treatment, alongside 332 healthy donor samples from 18 donors. A prospective cohort of 45 IBD patients provided 45 baseline stool samples, and a validation cohort of 112 non-IBD patients contributed 224 paired samples. Retrospective cohort patients were monitored for 4 weeks to assess FMT responsiveness and 52 weeks for treatment effectiveness. Microbiome analysis identified enterotype-specific bacteria and native bacterial genera influence FMT outcomes. Random forest, permissivity, and mathematical models predicted treatment response, characterized microbiome remodeling, and defined microecological remission thresholds. RESULTS: The FMT regimen was safe, with no serious adverse events reported. At week 4, the clinical response rates were 58.8% (26/45) for CD patients and 66.7% (34/51) for UC patients; by week 52, the remission rates were 82.4% (37/45) for CD patients and 84.4% (43/51) for UC patients. Microbiome analysis identified 54 bacterial genera linked to enterotype classification, 57 to UC response, and 93 to CD response. Notably, 38 high-frequency retentions of recipient native bacteria after FMT were predictive of FMT responsiveness. The permissivity model revealed a shift toward Bacteroidetes-dominated enterotypes in IBD patients post-FMT, which was validated in 112 non-IBD patients. The abundance ranges of recipients' native bacteria predictive of treatment responsewere determined by mathematical interpretation model. CONCLUSION: The patient's native microbiota significantly influences FMT efficacy in IBD, influencing microbiome remodeling and clinical outcomes, highlighting the importance of baseline microbial profiles in predicting FMT responsiveness and optimizing therapy.