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

Aya Osman; Simone Zuffa; Gemma Walton; Elizabeth Fagbodun; Panos Zanos; Polymnia Georgiou; Ian Kitchen; Jonathan Swann; Alexis Bailey

doi:10.1016/j.isci.2021.103048

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

iScience. 2021 Aug 28;24(9):103048. doi: 10.1016/j.isci.2021.103048. eCollection 2021 Sep 24.

Authors

Aya Osman^{1

2}, Simone Zuffa³, Gemma Walton⁴, Elizabeth Fagbodun⁵, Panos Zanos⁶, Polymnia Georgiou⁷, Ian Kitchen⁸, Jonathan Swann^{3

9}, Alexis Bailey⁵

Affiliations

¹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
³ Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
⁴ Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
⁵ Pharmacology Section, Institute of Medical and Biomedical Education, St George's University of London, London, UK.
⁶ Department of Psychology, University of Cyprus, 1 University Avenue, 2109 Nicosia, Cyprus.
⁷ Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, MD, USA.
⁸ School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
⁹ School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.

Abstract

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.

Keywords: Microbiome; Neuroscience; Nutrition.

Grants and funding

MR/N006321/1/MRC_/Medical Research Council/United Kingdom