Assessing the Safety and Efficacy of Fecal Microbiota Transplantation for Severe Chemotherapy‐Induced Diarrhea in Colorectal Cancer Patients: A Single‐Arm Clinical Trial

Background Diarrhea constitutes a significant complication among colorectal cancer (CRC) patients undergoing cytotoxic chemotherapy, impacting both their quality of life and treatment adherence. We aimed to assess the safety and efficacy of fecal microbiota transplantation (FMT) in severe chemotherapy‐induced diarrhea (CID) among patients with CRC. Materials and Methods We conducted an open‐label, single‐arm trial involving 20 patients with CRC experiencing severe CID (grade 2 or 3) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, in whom conventional standard antidiarrheal treatments were ineffective. Patients received a single course of orally administered FMT capsules, with a protocol allowing for a repeat course at a 2‐week interval if needed. Each course consisted of 90 capsules (10 capsules three times daily on Days 1, 2, and 3), delivering approximately 180 × 10 10 colony‐forming units (CFU) of bacteria. Patients were monitored for 12 weeks. The primary endpoint was the proportion of patients achieving a sustained clinical response (diarrhea reduced to less than six unformed bowel movements per day). Secondary endpoints included changes in gut microbiome composition and immune cell populations. Genomic analysis (16S rRNA gene sequencing) and immune cell phenotyping (flow cytometry) were performed on samples collected before and after FMT. Results The overall response rate, characterized by the improvement of diarrhea to less than six unformed bowel movements per day following one or more FMT procedures over a minimum period of 12 weeks, was noted in 85% (17/20) of patients (95% confidence interval [CI], [62.1%, 96.8%]). Genomic analysis demonstrated significant improvements in gut microbiome diversity after FMT. Moreover, it revealed significant alterations in immune cell populations post‐FMT. Specifically, we observed a statistically significant increase in CD19+ B cells ( p = 0.0001), CD3+ CD8+ T cytotoxic cells ( p = 0.0010), and natural killer (NK) cells ( p = 0.0002) following FMT treatment. No significant adverse events were reported. Conclusions These preliminary results suggest that FMT is a safe and potentially effective therapeutic approach for managing severe CID in the CRC patient population.