Fecal microbiota transplantation cannot induce remission after 8 weeks in adults with Crohn’s disease

The gut microbiota plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD), including both Crohn’s disease and ulcerative colitis, driving growing interest in therapies that target gut microbes as adjunctive or primary treatment. Among these, fecal microbiota transplantation (FMT) has attracted attention due to its remarkable success Clostridioides difficile infection¹ and promising results in mild to moderate ulcerative colitis (UC).²

A recent Canadian multicenter, double-blind, randomized controlled trial found FMT was ineffective in inducing endoscopic and clinical remission in mild to moderate Crohn’s disease (CD).³

Thirty-four adults with active celiac disease were enrolled at three major universities. Patients received initial FMT via colonoscopy followed by weekly oral capsules for seven weeks and were able to continue treatment with stable doses of oral 5-aminosalicylates, corticosteroids, immunomodulators, and biologics. The primary endpoint was combined clinical and endoscopic remission.

After eight weeks, none of the patients receiving FMT achieved combined clinical and endoscopic remission, while one patient in the placebo group did. However, despite a lack of remission, both the FMT and placebo groups experienced improvements in quality of life, and the FMT group showed a notable reduction in activity disturbances. This suggests that microbiome-targeted therapies may provide functional and symptomatic benefits to improve patient well-being even without achieving mucosal healing.

Microbiome analyzes revealed that patients who showed a clinical response had fecal microbial profiles more similar to those of their donors. This supports the concept that donor-recipient compatibility and microbial engraftment can determine therapeutic success. In clinical practice, this indicates the need for the development of personalized, microbiota-based medicinewhere donor selection or microbial composition can be tailored to patient-specific microbial profiles.

Importantly, the study showed that FMT is safe and well tolerated, with no serious side effects. This supports the continued exploration of FMT as part of combination regimens alongside biologics, small molecule therapies, and dietary therapies designed to improve microbial colonization and clinical response in patients with IBD.

The limitations of the study included the COVID-19 pandemic that affected enrollment and suspended the stool donor program, the short intervention period, and an intensive study regimen that required weekly clinical visits.

Overall, this study provides the most robust randomized evidence to date FMT alone is insufficient to induce short-term remission in active celiac disease the assumption that the success of FMT in ulcerative colitis can be extrapolated to CD. Achieving meaningful clinical responses through microbial modulation in patients with Crohn’s disease will likely depend on the future development of the disease personalized live biotherapeutics with defined communities of microbes and refined treatment protocols that can be tailored to address specific disease conditions.⁴ In short, the path forward likely involves an evolution from non-standardized and non-reproducible mixtures of microorganisms to precisely designed microbiome therapies tailored to each patient’s unique microbial profile.

References

1. Porcari S, Benech N, Valles-Colomer M, et al. Key determinants of success in fecal microbiota transplantation: from microbiome to clinic. Cell host microbe. May 10, 2023;31(5):712-733. Sunday: 10.1016/j.chom.2023.02.020
2. Chapon J, Scanzi J, Sokol H, Pereira B, Buisson A. Efficacy of different modalities of fecal microbiota transplantation in ulcerative colitis: systematic review and network meta-analysis. Therap Adv Gastroenterol. 2025;18:17562848251369624. doi:10.1177/17562848251369624
3. Kao D, Wong K, Jijon H, et al. Preliminary results from a multicenter, randomized trial using fecal microbiota transplantation to induce remission in patients with mild to moderate Crohn’s disease. Ben J Gastroenterol. Nov 12, 2024;120(6):1334-1344. doi:10.14309/ajg.0000000000003196
4. Mkilima T. Engineering artificial microbial consortia for personalized gut microbiome modulation and disease treatment. Ann NY Acad Sci. On June 2025; 154(1):29-5 Dos:10.1111, Niass.153