Beyond antibiotics: collateral damage to the gut microbiome during cancer therapy

Antibiotics are major drivers of microbiome disruption in oncology, but they do not fully explain the ecological changes observed during cytotoxic treatment. The central question of this Mini Review is when chemotherapy-associated microbiome change should be interpreted as transient compositional variation and when it constitutes a loss of ecosystem function with potential clinical consequences. We use collateral microbiome injury as a conceptual framework, rather than a formally established clinical diagnosis, to describe treatment-associated loss of microbial load, function, spatial organization, colonization resistance, or recovery capacity that is not required for antitumor activity. Three questions organize the review: which changes are directly attributable to a defined chemotherapeutic agent; which arise from the broader oncology exposome, including mucosal injury, antibiotics, nutritional disturbance, hospitalization, and supportive medications; and which ecological mechanisms are inferred from non-chemotherapy models. The evidence is therefore classified as direct chemotherapy evidence, oncology-exposome evidence, or general ecological evidence. Agent-specific studies support microbial transformation of irinotecan and fluoropyrimidines, whereas longitudinal leukemia studies more often capture composite treatment episodes. Across these settings, depletion of obligate anaerobe functions, altered nutrient and redox conditions, pathobiont domination, oral-to-gut niche coalescence, and impaired recovery may weaken colonization resistance. However, the strongest persistent-disruption and infection data arise from intensive hematologic treatment and should not be generalized uncritically to conventional solid-tumor chemotherapy. We propose operational criteria, multidimensional recovery metrics, and evidence-stratified translational priorities for moving from descriptive dysbiosis toward testable, microbiome-sparing supportive care.