This paper describes the protocol for a multicentre randomised controlled trial (TURN2) evaluating whether strictly anoxic-processed donor faecal microbiota transplantation is more efficacious than anoxic-processed autologous FMT in inducing steroid-free clinical and endoscopic remission in patients with mild to moderate active ulcerative colitis.
The TURN2 trial is designed as a randomised, double-blind, placebo-controlled, multicentre study comparing strictly anoxic-processed donor FMT versus anoxic-processed autologous FMT in active UC.
The previous TURN trial found a correlation between clinical response to FMT and specific microbial strains and butyrate production, motivating the design of TURN2.
Strict anoxic processing of donor stool is hypothesised to be essential for increasing FMT efficacy because most gut microbes, including many butyrate producers, are anaerobes.
The TURN2 trial employs a repetitive dual-route administration strategy, with patients receiving four weekly FMTs combining nasoduodenal and enema routes.
The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score, requiring 76 evaluable patients.
Donors are selected based on their microbiota profile, informed by findings from the previous TURN trial and the existing literature.
An interim analysis will be conducted midway through the study by an independent Data Safety Monitoring Board to monitor both efficacy and safety.
Secondary outcomes include clinical, endoscopic, and histological response, as well as evaluation of specific microbial strains, metabolites, and mechanisms correlated with response.
Mixed results and protocol heterogeneity across prior FMT studies in UC have limited practical application of FMT, providing the rationale for a standardised, optimised protocol in TURN2.
This paper describes the design and protocol for a clinical trial called TURN2, which tests whether faecal microbiota transplantation (FMT) — transferring stool from a healthy donor into a patient — can help people with mild to moderate ulcerative colitis (UC) go into remission. UC is a chronic inflammatory bowel disease, and research suggests that imbalances in the gut's microbial community play a role in causing it. A previous trial by the same team found that patients who responded to FMT tended to receive microbes that produced a molecule called butyrate, which has anti-inflammatory properties. Because these butyrate-producing microbes are sensitive to oxygen, TURN2 uses a careful oxygen-free ('anoxic') preparation process to keep them alive and effective. The TURN2 trial will randomly assign 76 patients to receive either donor FMT (from a carefully selected healthy donor) or autologous FMT (using the patient's own stool as a placebo). Patients will receive four weekly treatments, with some delivered through both a nasal tube into the small intestine and an enema, and others by enema alone. Donors are selected based on their microbial profiles, building on lessons from the previous trial. The main question the trial asks is whether patients achieve remission — defined as being free of steroids and having both clinical and endoscopic (camera-based) evidence of remission — at 8 weeks after starting treatment. Patients in the placebo group who do not respond will have the option to receive real donor FMT afterward. This research suggests that carefully optimising how FMT is prepared and delivered — by protecting oxygen-sensitive gut bacteria during processing, choosing donors with beneficial microbial profiles, and using multiple delivery routes repeatedly — may improve the chances of FMT working for people with UC. Beyond the clinical results, the trial will also collect detailed data on which specific microbes and their chemical products are linked to getting better, which could help develop more targeted treatments for inflammatory bowel disease in the future.
Bénard M, Van Der Spek M, Davids M, Visser C, Zoetendal E, Rethans B, et al.. (2026). Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised controlled trial (TURN2 study).. BMJ open. https://doi.org/10.1136/bmjopen-2025-107097