• Exercise reshapes microbiota function to enhance cancer therapy. • Exercise-gut axis improves immunotherapy, chemotherapy, and radiotherapy. • Microbiota functional state determines therapeutic response heterogeneity. • Physical activity optimizes host immune and metabolic responsiveness. Marked interindividual variability in cancer treatment outcomes indicates that traditional strategies focused solely on direct tumor cell eradication are insufficient to explain real world clinical responses. Host responsiveness to therapeutic stimuli has emerged as a critical determinant of efficacy. In recent years, the gut microbiota has been recognized as a central regulatory hub linking host immune and metabolic states with treatment outcomes. Through systemic modulation of immune activation thresholds, inflammatory tone, and tissue repair capacity, microbiota function participates deeply in shaping responses to immunotherapy, chemotherapy, and radiotherapy. Against the background of safety, stability, and personalization constraints associated with existing microbiota interventions, exercise has gained attention as a controllable endogenous physiological stimulus with long term feasibility. Regular physical activity reshapes the host metabolic milieu, strengthens intestinal barrier integrity, reduces basal systemic inflammation, and stabilizes immune homeostasis, thereby promoting a microbiota functional state that supports antitumor immunity. In this context, the host environment shifts from a passive background factor to an actively optimizable therapeutic variable. The regulatory axis formed by interactions between exercise and the gut microbiota provides a novel biological perspective for understanding treatment response heterogeneity across modalities and offers a unified functional rationale for enhancing immunotherapy responsiveness, improving chemotherapy tolerance, and facilitating radiotherapy associated tissue repair. Overall, integrating exercise into a host responsiveness centered therapeutic framework holds promise for amplifying treatment efficacy and improving long-term outcomes without altering existing oncologic regimens. With standardized study designs, refined functional assessment systems, and strengthened multidisciplinary collaboration, exercise mediated microbiota modulation is expected to progress from mechanistic exploration toward clinical implementation and become an integral component of comprehensive cancer therapy. Cancer therapy efficacy is strongly influenced by host responsiveness, which cannot be fully explained by tumor intrinsic factors alone. The gut microbiota serves as a central regulator linking immune activation, metabolic homeostasis, and tissue repair, thereby shaping responses to immunotherapy, chemotherapy, and radiotherapy. Exercise acts as a modifiable physiological stimulus that reshapes host metabolic and immune states, strengthens intestinal barrier integrity, reduces basal inflammation, and promotes a favorable gut microbiota functional profile. Through exercise-mediated microbiota remodeling, immune activation thresholds are lowered, antitumor immunity and immune memory are enhanced, drug metabolism and tolerance are improved, and tissue repair capacity is facilitated. Together, the exercise gut microbiota host axis provides a unified framework for enhancing therapeutic responsiveness, tolerance, and repair across cancer treatment modalities without altering standard oncologic regimens.
Fang et al. (Tue,) studied this question.