Human milk oligosaccharide supplementation in post-weaning rats fed a high fat/sucrose diet affects glutamate receptor gene expression in the nucleus accumbens and amygdala.

The consumption of human milk oligosaccharides (HMOs), a key component of breast milk, during early life has been shown to have long-lasting impacts on metabolic processes, immune system function, and nervous system development. The long-term effects of early-life HMO supplementation on behaviours that are associated with metabolic processes, such as food preferences and food choices, and mental health conditions, such as anxiety and depression, are less clear. The present study examined the effects of post-weaning supplementation with two common HMOs, 2'-fucosyllactose (2'FL) and 3'sialyllactose (3'SL), on anxiety-like behavior, sucrose consumption, food preference, and glutamate receptor gene expression in adulthood in Sprague-Dawley rats. We also assessed whether HMO supplementation could attenuate any changes in glutamate receptor gene expression or behavior associated with a high-fat/sucrose (HFS) diet. The present study demonstrated that the effects of HMO supplementation are both sex and dose-dependent, with changes in glutamate receptor gene expression in the nucleus accumbens (NAc) representing the most prominent changes. Effects on sucrose intake were modest and sex-specific, with H/HFS females consuming less sucrose than H/AIN females on the first, but not second, day of testing. This effect was most evident in females that received the high-HMO diet before the HFS challenge and was accompanied by lower GluR1 and GluR2 gene expression in the NAc. Rats fed a HFS diet displayed a preference for palatable food, regardless of early HMO exposure, which may be the result of changes to incentive salience or "wanting" for palatable foods. The findings of this study show a potential link between early-life HMO supplementation, behaviour, and the expression of genes related to synaptic plasticity.