Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

The postnatal period is critical for brain and behavioral development and is sensitive to environmental stimuli, such as nutrition. Prevention of weaning from maternal milk was previously shown to cause depressive-like behavior in rats. Additionally, loss of dietary casein was found to act as a developmental trigger for a population of brain opioid receptors. Here, we explore the effect of exposure to milk containing A1 and A2 β-casein beyond weaning. A1 but not A2 β-casein milk significantly increased stress-induced immobility in rats, concomitant with an increased abundance of Clostridium histolyticum bacterial group in the caecum and colon of A1 β-casein fed animals, brain region-specific alterations of μ-opioid and oxytocin receptors, and modifications in urinary biochemical profiles. Moreover, urinary gut microbial metabolites strongly correlated with altered brain metabolites. These findings suggest that consumption of milk containing A1 β-casein beyond weaning age may affect mood via a possible gut-brain axis mechanism.