Fecal Microbiota Transplantation (FMT) – some good news (C. difficile infection) and some disappointment (Ulcerative Colitis)

Review by Prof. Eamonn Quigley (USA)

Study Summary 

Fecal microbiota transplantation (or transfer) (FMT) is an ancient therapy that attained scientific validation in recent decades through the demonstration of its remarkable efficacy in the treatment of Clostridioides difficile infections (CDI). Traditionally, FMT was employed where first line therapy had failed and the patient had undergone two or more unsuccessful courses of treatment with antibiotics, such as metronidazole or vancomycin. If FMT was so successful, why wait until the patient had to endure recurrence? This question is addressed in the first of two studies included in the March 2025 issue of Clin Gastroenterol Hepatol.¹ These impressive results for FMT in CDI were not repeated in other diseases where the gut microbiome is thought to play an important role, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). For example, impacts in ulcerative colitis (UC) and IBS have ranged from clear benefits to no effect and even inferior outcomes. The second of these papers reports on a well conducted randomized controlled clinical trial of FMT in UC.

Paaske and colleagues report on the “real-world” efficacy on FMT in treating the first or second episode of CDI.¹ They enrolled 467 patients (average age 73 years) at multiple sites in Denmark presenting with their first or second episode of CDI. Even though 36% had antibiotic-refractory CDI, 56% severe CDI, and 19% fulminant disease, the overall cure rate following the first FMT was 76%, and for those who needed repeated FMTs, 79%. 90-day mortality was 10%.

Caenepeel and colleagues randomized 66 patients with moderate to severe to receive either anaerobic-prepared FMT of autologous FMT, delivered by flexible sigmoidoscopy or enema once weekly for four weeks with the primary endpoint being steroid-free remission at eight weeks.² The trial did not meet its primary endpoint and was terminated for futility.

Commentary 

These studies further emphasize the very contrasting disease-specific outcomes for FMT; great in CDI but value in UC yet to be confirmed despite some early encouragement.

Turning first to CDI, the results reported by Paaske and colleagues are impressive in view of the nature of the patients treated as well as the acuity and severity of their CDI. Their results, when viewed in the context of the expense of alternative approaches to severe or recurrent CDI, should certainly prompt a consideration of FMT as a first line option and, especially, for those with poor underlying health or a severe form of infection. Even though laudable attempts were made to optimize the donor material, no benefits were seen for FMT in UC. Why such disappointing results in the wake of prior optimism?  An accompanying editorial sheds some light and identifies disease severity, use of autologous FMT, absence of pre-FMT antibiotic treatment, and dose, frequency, and route of administration as possible confounders.³ The editorial writers suggest that future studies on FMT in UC should focus on mild-to-moderate disease and avoid severe cases.  

Citation

1. Paaske SE, et al. Real-world effectiveness of fecal microbiota transplantation for first or second Clostridioides difficile infection. Clin Gastroenerol Hepatol 2025;23:616-8.
2. Caenepeel C, et al. Rigorous donor selection for fecal microbiota transplantation in active ulcerative colitis: key lessons from a randomized controlled trial halted for futility. Clin Gastroenerol Hepatol 2025;23:621-31.
3. Claytor JD, Faith JJ. Fecal microbiota transplantation (FMT) in ulcerative colitis: holding out for a superdonor. Clin Gastroenerol Hepatol 2025;23:602-11.

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