Systematic review finds FMT and standardized microbiome products outperform antibiotics in efficacy and safety.
A systematic review published in Cureus found that fecal microbiota transplantation (FMT) and standardized microbiome therapeutics such as SER-109 and RBX2660 demonstrate significantly higher cure rates and favorable safety profiles compared with standard antibiotic therapy for recurrent Clostridium difficile infection (rCDI).1
Across 7 studies involving 1030 patients, FMT achieved clinical cure rates of 70% to 91%, compared with 23% to 62% for antibiotics or placebo. Donor FMT outperformed autologous FMT (90.9% vs 62.5%; P = .042) and standard regimens, including fidaxomicin (33% resolution) and vancomycin (19%; P < .01). Microbiota-based products showed similar efficacy, with relative risk reduction of recurrence up to 68%. Safety outcomes were favorable over a 5-year follow-up, with most adverse events limited to mild gastrointestinal symptoms and no new safety concerns identified.1
The review followed PRISMA 2020 guidelines and included 6 randomized controlled trials and one cohort study published between January 2015 and May 2025. Bias assessments were conducted with the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies. Heterogeneity in administration routes (capsules vs colonoscopy) and donor material (fresh vs frozen) was noted.1
Investigators concluded that FMT and standardized microbiome-based therapies provide highly effective treatment options for patients with recurrent or refractory CDI. They emphasized the need for further research to standardize treatment protocols and evaluate outcomes in higher-risk populations.1
In seven studies (N = 1030), FMT achieved cure rates of 70% to 91% compared with 23% to 62% for antibiotics or placebo.
Donor FMT and microbiome-based products (SER-109, RBX2660) reduced recurrence risk by up to 68%, with favorable safety outcomes over 5 years.
Authors highlight the need for standardized protocols and further research in high-risk patient populations.
This emphasis on microbiome therapies reflects a broader trend in 2025, with multiple studies highlighting both opportunities and challenges. For example, Clemson University researchers reported in mBio that FMT failures may stem less from microbial engraftment and more from functional incompatibility between donor microbes and the recipient gut environment. In mouse models, human donor stool successfully colonized but failed to clear Clostridioides difficile, whereas mouse donor stool proved effective. These findings help explain why up to 10% of rCDI patients do not respond to FMT, and why failure rates are even higher in more complex conditions such as inflammatory bowel disease or irritable bowel syndrome.2
In addition, a large real-world cohort study from Aarhus University Hospital examined more than 1100 adults treated with FMT between 2016 and 2023. The most successful strategies involved administering FMT via multiple-dose capsules or colonoscopy after prolonged antibiotic pretreatment, with repeated FMT outperforming antibiotics alone for recurrent cases. Overall, 81% of patients achieved cure by 8 weeks, supporting clearer guidance on FMT dosing, delivery, and pretreatment duration.3
Together, these studies illustrate a consistent trend in rCDI research this year: while FMT and microbiome-based products are proving highly effective and generally safe, optimizing their functional compatibility, delivery strategies, and treatment protocols remains essential for maximizing clinical benefit.
