Exercise prescription for mood and cognition: targeting the microbiota-gut-brain axis through short-chain fatty acids

Scientific study has extensively corroborated the advantageous impacts of exercise on mood, cognitive function, and stress resilience. Nonetheless, the fundamental biological mechanisms underpinning these effects have yet to be thoroughly integrated. This review advocates for and substantiates an integrated model focused on the "Exercise-Gut Microbiome-Short-Chain Fatty Acids (SCFAs)-Brain Function" axis. Consistent physical exercise alters the gut microbiota, enhancing Short-Chain Fatty Acid (SCFA)-producing populations, which is associated with markedly elevated bioavailability of key metabolites (acetate, propionate, and butyrate). Rather than detailing exhaustive molecular pathways here, we emphasize that these SCFAs facilitate gut-brain communication through multiple synergistic routes, including receptor-mediated neuroendocrine signaling, epigenetic modulation of neuroplasticity, and the attenuation of systemic neuroinflammation. Current human observational and interventional data strongly support an associative link between exercise-induced SCFA fluctuations and improved mental health outcomes. Crucially, we propose the novel "Exercise × Fiber Synergy" hypothesis: exercise primes the intestinal ecological niche for efficient substrate-utilizing bacteria, while adequate fermentable dietary fiber provides the necessary raw materials. Synergistically, this combination optimizes SCFA production to maximize cognitive and emotional benefits. To transition this framework into clinical practice, future research must prioritize 2 × 2 factorial designs (Exercise × Fiber) with dynamic kinetic measurements, paving the way for microbial phenotype-oriented precision exercise and personalized nutritional interventions to enhance public mental health.