A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF PSYLLIUM FIBER AND FECAL MICROBIOTA TRANSPLANTATION FOR MILD TO MODERATE ULCERATIVE COLITIS

Abstract

Abstract BACKGROUND Emerging clinical data shows potential for fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), though factors affecting clinical response remain poorly defined. Pre-clinical data suggest the role of dietary fiber in enhancing microbial metabolites to mitigate colitis severity. This study aimed to evaluate the role of the prebiotic psyllium in improving the clinical outcomes of FMT for mild to moderate UC, with the long-term goal of enhancing FMT as a therapeutic strategy for UC. METHODS In a randomized, placebo-controlled clinical trial, 32 participants were screened, and 27 adults with mild to moderate UC were enrolled. Baseline fiber intake was assessed through a food frequency questionnaire. Subjects were randomly assigned to receive FMT alone, FMT with daily fiber (10g of psyllium), or a placebo with or without fiber. The primary endpoint was clinical response by Mayo score at week 8. Secondary endpoints included clinical response by partial Mayo (pMayo) score, endoscopic sub-score, and clinical remission. At week 8, participants underwent crossover treatment with clinical evaluation at week 12. The study ended early due to the manufacturer discontinuing fecal microbiota preparation supply. RESULTS Analysis of primary and secondary endpoints in "FMT alone" and "FMT with fiber" groups revealed no statistically significant differences in clinical response (55.56% alone, N=9 vs. 22.22% fiber, N=9, p=0.1686). Participants with low and high dietary fiber consumption had similar response rates, regardless of supplemental fiber. Consequently, we combined the "FMT" and "no FMT" groups, which showed a significantly higher proportion of subjects achieving clinical response in the FMT group as defined by the partial Mayo score (50.00% FMT group (N=18) and 11.1% in the no FMT group (N=9), p=0.0485). A similar trend was observed for clinical response as defined by the total Mayo score and endoscopic sub-score, where the FMT group outperformed the placebo (38.89% FMT, N=18, vs. 11.11% placebo, N=9, p=0.1362). Among the 9 subjects who received FMT at week 0 and exhibited clinical response defined by pMayo, 77.8% (n=7) maintained their response at week 12. Additionally, 2 patients who initially had no response at week 8 achieved a clinical response by week 12. CONCLUSION The results demonstrate a robust effect of single-dose FMT via colonoscopy in a mild to moderate UC cohort. Given the low cohort size, our results lack the statistical power to reveal the clinical impact of fiber supplementation in FMT. Notably, a substantial proportion of initially responsive FMT recipients maintained their clinical response at week 12, indicating the potential for sustained benefits. Microbiome and metabolomic analyses are currently underway to assess the functional impact of dietary fiber in shaping the effectiveness of FMT for UC.