Donor Composition and Fiber Promote Strain Engraftment in a Randomized Controlled Trial of Fecal Transplant with Dietary Fiber for Ulcerative Colitis (MINDFUL)

Background: Fecal microbiota transplantation (FMT) is an emerging treatment for ulcerative colitis (UC), but the impact of prebiotic fiber on FMT efficacy for UC is unclear. We performed a randomized, placebo-controlled clinical trial to examine the efficacy of FMT with and without dietary fiber supplementation in patients with UC.Methods: 27 patients with mild to moderate UC were randomized to receive a single FMT or placebo via colonoscopy with or without psyllium fiber supplementation for 8 weeks. The primary outcome was clinical response at week 8 assessed by Mayo score. Secondary outcomes included endoscopic improvement and clinical remission. Metagenomic sequencing of fecal DNA was analyzed to determine taxonomic profiles and donor strain engraftment.Results: FMT, with or without daily fiber supplementation, induced clinical response, remission, and endoscopic improvement in UC patients compared to placebo, but fiber did not improve clinical outcomes of FMT. Recipient microbiome composition post-FMT shifted towards donor composition in responders and non-responders, but the durability of this change was stronger in responders. Donor-dependent differences accounted for clinical success, magnitude of the shift in recipient microbiome, and successful engraftment of strains correlating with clinical improvement. Fiber supplementation enhanced strain-level engraftment.Conclusions: Single-dose FMT demonstrated robust clinical efficacy for mild to moderate UC compared to placebo but revealed no clinical impact of fiber supplementation. These results highlight proof-of-concept that donor selection and prebiotic fiber can shape strain level engraftment.