Clinical bottom line
Microbiome-based therapies, including fecal microbiota transplantation (FMT) and defined microbial consortia, are emerging as promising adjuncts in managing recurrent Clostridioides difficile infection (rCDI) and potentially other infectious complications in patients receiving novel cancer therapies. Early evidence suggests these interventions may restore gut microbial balance, reduce infection recurrence, and modulate immune responses. However, clinical experience remains limited, and risks such as pathogen transmission and unpredictable immune effects warrant cautious application. Infectious disease clinicians should consider microbiome-based therapies primarily in refractory rCDI cases while monitoring evolving data on broader infectious indications and safety profiles.
What the evidence shows
Recurrent Clostridioides difficile infection remains a significant clinical challenge, particularly in patients with disrupted gut microbiota due to antibiotics or immunosuppressive cancer therapies. Microbiome-based therapies have demonstrated efficacy in reducing rCDI recurrence by restoring microbial diversity and colonization resistance. Barrett et al. (2014) highlighted the importance of managing toxicity and infection risk in patients receiving novel T-cell engaging therapies, underscoring the potential role of microbiome modulation in this vulnerable population. Chauhan et al. (2022) and Berry et al. (2023) provide comprehensive reviews supporting the use of FMT and emerging microbial consortia as effective interventions for rCDI, with favorable safety profiles in carefully selected patients.
Beyond rCDI, microbiome dynamics may influence susceptibility to bloodstream infections during cancer treatment. Stamper et al. (2025) employed a perturbation-aware neural ODE model to predict gut-borne bloodstream infections in patients undergoing cancer therapy, suggesting that microbiome monitoring could inform infection risk stratification and targeted interventions. Sadiq et al. (2021) discuss the putative role of microbiome-based therapies in viral infections, proposing immunomodulatory benefits that could extend to infection prevention or mitigation in immunocompromised hosts.
However, the risk of invasive fungal infections remains a concern in patients receiving novel therapies, as reported by Hsu et al. (2015) in multiple myeloma cohorts. While microbiome interventions may theoretically reduce fungal colonization by restoring bacterial-fungal balance, robust clinical data are lacking. Similarly, Mustafayev et al. (2022) document viral reactivation risks (HBV, HCV) in cancer patients on novel agents, highlighting the complexity of infection management where microbiome-based therapies might play an adjunctive but unproven role.
Caveats and uncertainty
Current evidence for microbiome-based therapies outside rCDI is largely hypothesis-generating or derived from small observational studies and computational models. The heterogeneity of microbial preparations, lack of standardized protocols, and variable patient immune status complicate interpretation and generalizability. Safety concerns include the potential transmission of multidrug-resistant organisms or occult pathogens through FMT, as well as unpredictable immune activation or suppression in immunocompromised hosts.
Moreover, the timing, dosing, and patient selection criteria for microbiome interventions in the context of novel cancer therapies remain undefined. The interplay between microbiome alterations and infection risk is complex and influenced by multiple factors including chemotherapy, immunotherapy, antibiotic exposure, and host genetics. Thus, microbiome-based therapies should not replace established infection prevention and treatment strategies but may serve as complementary approaches pending further validation.
How this may change practice
Infectious disease clinicians managing patients receiving novel cancer therapies should remain aware of microbiome-based therapies as an evolving tool, especially for refractory rCDI. Incorporating microbiome assessment and consultation with specialized centers offering FMT or microbial consortia could optimize outcomes in selected cases. Integration of microbiome dynamics into infection risk prediction models, as pioneered by Stamper et al. (2025), may soon enable personalized infection prophylaxis strategies.
Future practice may expand microbiome-based interventions to prevent or mitigate bloodstream infections, fungal infections, and viral reactivations in immunocompromised patients, but this requires rigorous clinical trials. Meanwhile, clinicians must balance potential benefits against risks, ensuring informed consent and adherence to emerging safety guidelines. Multidisciplinary collaboration among infectious disease specialists, oncologists, and microbiome researchers will be critical to safely translate these promising therapies into routine care.