Effects of Different Cow-Milk Beta-Caseins on the Gut-Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies.

The gut and brain communicate through bidirectional neural, endocrine, and immune signals to coordinate central nervous system activity with gastrointestinal function. Dysregulated inflammation can promote immune cell activation and increase entero-endocrine signaling and intestinal permeability; hence, a functional gut-brain axis is necessary for a healthy digestive system. The consumption of milk products can lead to gut discomfort via effects on gastrointestinal tract function and the inflammatory state, which, in turn, affect the brain. A1 β-casein and A2 β-casein are major components of bovine-milk protein, and their digestion may result in different physiological effects following the consumption of milk products. Peptides derived from A1 β-casein, such as β-casomorphins, may increase gut dysfunction and inflammation, thereby modulating the availability of bioactive metabolites in the bloodstream and contribute to changes in cognitive function. This narrative review examines the functional interrelationships between the consumption of cow-milk-derived β-caseins and their effect on the brain, immune system, and the gut, which together comprise the gut-brain axis.