S2120 Using Oral Capsules for FMT Is as Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Recurrent Clostridioides difficile infection (rCDI) poses a significant challenge for clinicians and is the primary indication for fecal microbiota transplantation (FMT), increasing U.S. healthcare spending by over $1 billion. Yet most centers still rely on colonoscopy or enema delivery for FMT—procedures that are invasive, resource-intensive, and poorly tolerated. Oral, freeze-dried FMT capsules promise guideline-shifting convenience, but concerns persist that capsule transit or gastric acidity might blunt efficacy or raise safety risks. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified randomized controlled trials (RCTs) comparing oral FMT capsules in comparison to freeze dried FMT via enema or placebo up to the large randomized MATCH 2025 study. Data were analyzed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using RoB 2.0. Results: In 3 eligible RCTs (n = 323; oral-capsule FMT = 160, comparators = 163) adverse-event, mortality, and recurrence rates were indistinguishable between delivery routes. Any treatment-related adverse event occurred in 13.1% of capsule recipients’ vs 16.0% of controls (RR 0.83, 95% CI 0.50–1.38; P = 0.47; I² = 0%), with no effect-modification when trials were stratified by active-route vs placebo comparator (interaction P = 0.92). All-cause mortality was numerically lower with capsules (1.9% vs 3.7%; RR 0.71, 0.22–2.32), though precision was limited and heterogeneity modest (I² = 37%; interaction P = 0.09). Recurrent C. difficile infection ≤8 weeks occurred in 8.1% vs 8.0% (RR 1.04, 0.50–2.15; I² = 0%), again with no subgroup signal (interaction P = 0.64). Conclusion: Capsule FMT was non-inferior to invasive delivery or placebo in rCDI, showing identical recurrence rates and no increase in adverse events or mortality. The zero to low heterogeneity and consistent subgroup signals confirm that convenience does not come at the cost of efficacy or safety. Adopting capsules could spare patients procedural risks, slash endoscopy-suite burden, and broaden FMT access—particularly in outpatient or resource-limited settings. Large pragmatic trials and cost-effectiveness analyses should now focus on how to best integrate capsule FMT into patient care pathways.