Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review
Demi Wekking, Tom van den Ende, Maarten F. Bijlsma, Andrés Vidal-Itriago, Max Nieuwdorp, Hanneke W.M. van Laarhoven
Abstract
BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action. METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen. RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration. CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.