BERLIN — Anaerobic preparation and careful donor selection could be key to realizing the full potential of fecal microbiota transplantation (FMT) in ulcerative colitis (UC), according to results from the TURN2 randomized controlled trial.

“We wanted to see whether optimizing the process, especially anaerobic preparation and donor selection, could improve consistency and efficacy,” said Florine Zwezerijnen-Jiwa, MD, of Amsterdam University Medical Centre, Amsterdam, the Netherlands, who presented the results here at the United European Gastroenterology (UEG) Week 2025.

In the study, 23% of patients receiving donor FMT achieved steroid-free clinical remission at 8 weeks compared with 5% of participants who received autologous FMT.

“The findings point to a meaningful gain in UC remission rates compared with autologous transplantation, and hint at how standardizing FMT methodology could shift its role in the UC treatment landscape,” said Zwezerijnen-Jiwa.

Reducing the Variation in FMT Outcomes in UC

With FMT, “we take the approach of restoration of the gut homeostasis rather than suppression of inflammation,” Zwezerijnen-Jiwa explained. The procedure has shown promise for UC, but outcomes have varied widely between studies.

In this multicenter study, the team optimized every step of the FMT process, from anaerobic stool handling to dual-route delivery (nasoduodenal administration combined with an enema, and two single enemas) and donor prescreening, with the goal of maximizing microbial viability and treatment response.

The TURN2 study randomly assigned 85 patients with mild-to-moderate UC to receive either donor FMT or autologous FMT (their stool) prepared under strictly anaerobic conditions. Each patient received four treatments over 4 weeks, with one treatment per week.

Participants had a mean age of 43 years and a disease duration of around 8 years. About 75% had E2 disease extent, and around 70% took concomitant medication (with approximately 60% on oral mesalamine).

Donors were chosen based on their microbiota profiles, drawing on microbial signatures associated with sustained remission. “We carefully selected donors who had the bacterial profiles we believed were most likely to induce remission,” said Zwezerijnen-Jiwa. “It’s not just about a healthy donor; it’s about a microbiologically optimized donor.”

The primary endpoint of steroid-free clinical remission at 8 weeks — defined by an adapted Mayo score ≤ 2 — was reached by 23% of patients (10/44) receiving donor FMT compared with 5% in the autologous group (2/38; P = .028). These results apply to the modified intention-to-treat analysis where all patients received at least one FMT treatment (n = 82).

“Although these are modest numbers, the difference between donor and autologous FMT was statistically significant and clinically meaningful,” Zwezerijnen-Jiwa noted. “It tells us that the biology of the donor really matters and that anaerobic processing likely preserves bacteria that are crucial for therapeutic effect.”

A total of 26 patients who received autologous FMT in the initial 8-week part of the study went on to receive donor FMT in an open-label extension up to 52 weeks. A total of 21 (81%) received all four treatments, with 7/26 (27%) reaching the primary endpoint.

Anaerobic Preparation, Dual-Route Administration

Most gut microbes are strict anaerobes that die quickly on exposure to oxygen, yet historically, most FMT processing has been performed under ambient conditions. TURN2 used an anaerobic chamber and processing pipeline designed to preserve these sensitive bacteria.

“When we expose stool to oxygen, many of the bacteria that may be therapeutically important simply don’t survive,” said Zwezerijnen-Jiwa. “By keeping the process oxygen-free from start to finish, we believe we’re maintaining microbial diversity and functionality, and that could explain the better outcomes.”

She added that this technical refinement could be one reason for the variability in previous FMT trials for UC. “Anaerobic processing is logistically more complex,” she said, “but our findings suggest it’s worth the effort.”

To maximize mucosal exposure, the researchers used both upper and lower gastrointestinal routes for initial administrations. “Ulcerative colitis affects the entire colon, and bacteria need to reach distal and proximal areas to recolonize effectively,” said Zwezerijnen-Jiwa. “Dual-route administration ensures a broader distribution of donor microbiota.”

Adherence was high, with 89% of patients completing all four treatments in the 8-week part of the study. Adverse events were mostly mild. Two were considered treatment-related, with one case of pneumothorax after nasoduodenal tube placement and one overnight hospitalization for abdominal pain. “Overall, the protocol was safe and feasible,” said Zwezerijnen-Jiwa.

Microbial analyses are ongoing to identify bacterial taxa associated with response. Early data point to an increased abundance of short-chain fatty acid-producing species, echoing earlier TURN trial findings linking butyrate metabolism with mucosal healing.

“We’re now performing deep microbiome and metabolome analyses to pinpoint which microbes and metabolites correlate with remission,” she said. “Understanding these relationships could ultimately allow for a more targeted or even synthetic microbial therapy.”

Ultimately, the TURN2 study systematically addresses biological and procedural aspects of FMT and marks a step towards precision microbiome therapy.

“It’s not just transferring stool,” said Zwezerijnen-Jiwa. “It’s about transferring the right microbes in the right way, under the right conditions. The details really matter.”

A ‘Daring’ Study

Commenting on the results, Wouter de Jonge, PhD, also from the Amsterdam University Medical Centre but who was not involved in the research, called it a “daring” study. 

“FMT is an area that is logistically and operationally difficult to manage,” he said. “For example, it can be challenging to define the control group — it isn’t a simple randomized, controlled small molecule trial. Here, the patient needs to undergo a series of treatments. However, the outcome of this study tells us a lot about the importance of the microbiome in ulcerative colitis.”

Overall, these results “show promise, in that patients having anaerobic FMT and ‘selected’ donors showed statistically improved remission rates compared to those receiving autologous FMT,” said Benjamin Mullish, MB BChir MA, PhD, Senior Clinical Research Fellow in the Division of Digestive Diseases, Imperial College London, London, England.

However, he added, “It is difficult to gauge the additive value of this extra work in anaerobic processing and focused donor selection, since there was no arm of this study using more conventional aerobic processing or ‘routine’ donor selection to compare with.”

He also reflected that there was still substantial research to be done in the field due to “the relatively low rates of remission seen (under 30% in the treatment group), implying that there may be other clinical and biological factors that we have to consider yet for the optimal selection of donors and administration of FMT within the UC setting.”

Zwezerijnen-Jiwa, De Jonge, and Mullish have not declared any financial disclosures.