Examining the role of fecal microbiota transplantation for inducing remission in resistant ulcerative proctitis and distal ulcerative colitis (ulcerative proctitis-fecal microbiota transplantation)

IMPORTANCE: Resistant ulcerative proctitis (UP) represents a clinical conundrum, often necessitating the use of systemic therapy despite the disease being localized. Fecal microbiota transplantation (FMT) has proven efficacy for inducing remission in ulcerative colitis (UC) but has not been evaluated in UP. OBJECTIVES: To assess the safety and efficacy of FMT enema therapy for resistant UP. DESIGN: Single-arm open-label pilot study. SETTING: The Queen Elizabeth Hospital, Adelaide, Australia. PARTICIPANTS: Thirty patients with active UP or distal UC (total Mayo 3-10 with endoscopic Mayo subscore ≥1), with maximal disease extent up to ≤3030 cm from anal verge). INTERVENTIONS: Vancomycin conditioning and dietary education, followed by six anaerobically prepared single-donor FMT retention enemas administered over 8 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was safety and tolerability of FMT therapy. Secondary endpoints included combined clinical and endoscopic remission (Mayo Clinic score ≤2 with endoscopic subscore ≤1), histological remission, patient-reported outcomes, and exploratory microbial analysis. RESULTS: Thirty participants were enrolled (median age 41 years; 17 [57%] female). Serious adverse events occurred in 3 patients, including flare of UC (n = 2) and Clostridioides difficile colitis (n = 1). Eighteen patients (60%) reported mild-moderate adverse events, most commonly gastrointestinal symptoms. Combined clinical and endoscopic remission was achieved in 10 patients (33.3%). Higher baseline Mayo score (odds ratio [OR]: 0.28, P = .008) and fecal calprotectin (OR: 0.66, P = .049) predicted failure to achieve remission. Participants demonstrated a decrease in Shannon diversity (P = .02) following the dual intervention of vancomycin conditioning and FMT. CONCLUSIONS AND RELEVANCE: Antibiotic conditioning followed by FMT enema therapy was well tolerated and demonstrated efficacy in inducing clinical remission in UP. Further controlled studies of FMT in UP are warranted alongside a mechanistic assessment of both fecal and mucosa-associated microbiome.