The accelerating aging of the global population has rendered age-related multimorbidity a significant public health challenge. Conventional polypharmacy strategies exhibit limitations, creating an urgent need for multi-targeted, non-pharmacological interventions. The gut-brain axis (GBA), a bidirectional communication pathway linking the gut microbiota and the central nervous system, plays a pivotal role in the pathogenesis of aging and associated chronic diseases. This review systematically explores the potential mechanisms and clinical evidence supporting exercise - a safe, economical, and non-pharmacological intervention- in ameliorating age-related multimorbidity through the modulation of the GBA. Focusing on exercise-induced regulation of the gut microbiota composition, intestinal barrier function, neural signaling pathways, and systemic inflammation, this article analyzes the integrative role of exercise in various multimorbidity patterns, including neuro-cardiovascular, metabolic-sarcopenic, and psycho-sleep multimorbidity. Current evidence indicates that moderate-intensity aerobic exercise, resistance training, high-intensity interval training, and mind-body exercises can synergistically improve the multimorbidity status by increasing beneficial microbiota, elevating short-chain fatty acid (SCFA) levels, enhancing brain-derived neurotrophic factor (BDNF) expression, and suppressing chronic inflammation. Future high-quality clinical trials are warranted to optimize personalized exercise prescriptions and promote their application in the precision management of age-related multimorbidity.
Chen et al. (Sun,) studied this question.
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