In recent years, the gut microbiome has been increasingly recognized as a key modifiable determinant of both the efficacy and safety of anticancer therapy. Growing clinical and experimental evidence indicates that microbial community structure and, more importantly, functional capacity can shape systemic immune tone, inflammatory signaling, and host–microbe metabolic outputs (including short-chain fatty acids, tryptophan-derived metabolites, and bile acid transformation). Through these pathways, the microbiome may influence tumor immune microenvironment features and the likelihood of response or resistance to modern treatments, particularly immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4. In parallel, the microbiome can contribute to treatment-related toxicity by modulating drug metabolism and mucosal immunity, thereby affecting the risk and severity of immune-related adverse events (irAEs) and gastrointestinal complications. This article synthesizes current mechanistic concepts and translational findings linking the microbiome to oncologic outcomes and evaluates microbiotechnology-driven strategies for targeted microbiome modulation, including fecal microbiota transplantation, live biotherapeutic products (defined microbial consortia), prebiotic and postbiotic interventions, metabolite-oriented approaches, and selective inhibition of specific bacterial enzymes as a rational route to reduce toxicity while preserving anticancer activity. Particular attention is paid to practical barriers to implementation—standardization, biosafety, reproducibility, regulatory requirements, and major confounders such as antibiotic exposure, diet, and concomitant medications—which complicate causal inference and limit broad clinical adoption. Overall, the evidence supports the promise of personalized, biomarker-informed microbiome modulation as an adjunct strategy to enhance therapeutic benefit and mitigate adverse effects, provided that efficacy and safety are confirmed in well-controlled clinical trials.
Xabibullayev et al. (Mon,) studied this question.