摘要：SummaryThe 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 ofClostridium histolyticumbacterial 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.Graphical abstractDisplay OmittedHighlights•Postnatal brain development is sensitive to nutritional exposures•Consumption of A1 but not A2 β-casein milk post-weaning affects mood in rats•Gut microbial, biochemical, and neurochemical changes accompany mood alterations•Urinary gut microbial metabolites correlate with brain metabolitesNutrition; Neuroscience; Microbiome
