Microbiota-mediated gut-brain communication following whey protein supplementation and resistance training: current evidence linking gastrointestinal function and cognitive health.

Whey protein supplementation in conjunction with resistance training (RT) has emerged as a promising strategy that may modulate microbiota-mediated gut-brain communication, with potential implications for gastrointestinal (GI) function and cognitive health. Evidence from both preclinical and clinical studies suggests that whey protein supplementation and exercise, including RT, may influence gut microbial composition and function through changes in substrate availability, intestinal physiology, and host-microbe interactions. Whey protein supplementation has been associated with source-dependent changes in gut microbial communities, including alterations in the abundance of Bacteroidetes, Bifidobacterium, and butyrate-producing taxa, whereas exercise particularly aerobic exercise, with more limited evidence for RT-has been associated with greater microbial diversity and an increased abundance of short-chain fatty acids (SCFAs)-producing bacteria. Although direct evidence evaluating the combined effects of whey protein supplementation and RT remains limited, available findings suggest that their combination may influence microbial metabolic activity in addition to microbial composition. Microbiota-derived metabolites, particularly SCFAs, together with exercise- and whey protein-induced changes in gut hormone secretion, including glucagon-like peptide-1, peptide YY, and cholecystokinin, may represent plausible mechanistic links between the GI tract and the central nervous system. These pathways may contribute to the regulation of intestinal barrier integrity, neuroendocrine communication, immune responses, and neuroplasticity. Experimental evidence further suggests that whey protein supplementation combined with exercise, including RT, may contribute to reduced oxidative stress and neuroinflammation and may support brain-derived neurotrophic factor signaling; however, direct evidence linking microbiota-mediated changes to cognitive outcomes in combined intervention studies remains scarce. Nevertheless, findings remain heterogeneous because of differences in protein dosage, exercise protocols, intervention duration, study populations, and individual microbiome variability. Overall, current evidence supports the biological plausibility of microbiota-mediated gut-brain communication as a potential mechanism underlying the effects of whey protein supplementation and RT; however, well-designed human studies directly evaluating gut microbiota, gut-brain signaling, and cognitive outcomes are needed to confirm these proposed relationships.