Examining the role of faecal microbiota transplantation for inducing remission in resistant ulcerative proctitis and distal ulcerative colitis (up-FMT).

Abstract

Background: Resistant ulcerative proctitis (UP) represents a clinical conundrum, often necessitating the use of systemic therapy despite the disease being localised. Faecal microbiota transplantation (FMT) has proven efficacy for inducing remission in ulcerative colitis (UC) but has not been evaluated in UP.

Aims: To undertake a pilot study examining the safety and efficacy of FMT enema therapy for management of resistant UP.

Methods: Patients with mild-moderate active UP (total Mayo 3-10 with endoscopic Mayo subscore ≥ 1) were enrolled. After an initial conditioning phase of vancomycin and dietary education, participants received six anaerobically prepared single-donor FMT retention enemas over 8 weeks. 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: 30 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). 18 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 (OR 0.28, p = 0.008) and faecal calprotectin (OR 0.66, p = 0.049) predicted failure to achieve remission. Participants demonstrated a decrease in Shannon diversity (p = 0.02) following the dual intervention of vancomycin conditioning and FMT.

Conclusions: 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 mechanistic assessment of both faecal and mucosa-associated microbiome.