Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which neuroinflammation, vascular dysfunction, metabolic disturbances, and impaired tissue resilience contribute to disease progression. Aerobic exercise is a widely applicable lifestyle intervention that has been increasingly investigated in AD; however, the mechanisms linking peripheral exercise adaptations to brain outcomes remain incompletely understood. This review evaluates the potential contribution of gut-derived signaling within the broader multisystem response to aerobic exercise, focusing on evidence strength, causal interpretation, and translational limitations. Current evidence suggests that aerobic exercise is associated with alterations in gut microbial features, microbial-derived metabolites, intestinal barrier-related processes, peripheral inflammatory signaling, and brain-relevant responses. Preclinical studies, mainly from AD mouse models, provide biological plausibility that microbiota-related factors may contribute to exercise-associated modulation of neuroinflammation, amyloid-β and tau pathology, and cognitive outcomes. However, microbiota-targeted interventions provide only partial support for causal involvement because of limited specificity and ecological constraints. Human studies support exercise-associated improvements in cognitive, metabolic, inflammatory, and functional outcomes, but direct evidence that gut-derived alterations mediate these benefits remains unavailable. Overall, aerobic exercise should be viewed as a multisystem physiological stimulus rather than an intervention acting through a single gut-mediated pathway. Gut-derived signals represent plausible candidate interfaces that interact with vascular, metabolic, neurotrophic, immune, and neurovascular mechanisms. Future longitudinal and mechanistic studies integrating multi-compartment measurements and pathway-specific perturbation are required to determine whether gut-related alterations represent mediators, consequences, or parallel adaptations of exercise-associated benefits in AD.
