Nutritional interventions targeting the microbiota‐gut‐brain axis may be able to modulate stress‐induced dysfunction of physiological processes and brain development. Maternal separation (MS) stress of rat pups is a robust model of early life stress that induces long‐term alterations to behavior and brain neurochemistry. In this study the effects of milk fat globule membrane (Lacprodan MFGM‐10®, 15 g/kg) and a polydextrose / galactooligosaccharide (7 g/kg each) prebiotic blend were evaluated on early life stress induced alterations. The maternal separation protocol was conducted as described in O'Mahony et al., 2009. Rats were separated from their mothers for 3 h /day from postnatal day (PND) 2 to 12. Starting at weaning (PND 21), both non‐separated (NS) and maternally separated (MS) offspring were randomized into separate experimental groups and were provided drinking water with or without supplementation of MFGM, prebiotic blend or a combination of both. Visceral sensitivity was assessed using the colorectal distension test conducted at PND 79. MS rats demonstrated visceral hypersensitivity to colorectal distension reflected by a lower pain threshold and a higher number of pain behaviours when compared to NS rats. This increase in sensitivity in MS rats was ameliorated by MFGM (p=0.01) and also the combination of MFGM and the prebiotic blend (p=0.045). Furthermore, MS rats showed significant impairments in spatial and reference memory in the Morris water maze, which was carried out between PND 61–65. Cognitive performance in this test was improved by the prebiotic blend (p=0.007) and MFGM alone (p=0.019) as well as the combination of both (p<0.0001). Interestingly, the combination of MFGM and prebiotic reversed the impact of early life stress on the mineralocorticoid receptor (MR) expression in the hippocampus, which is associated with negative feedback of the hypothalamic pituitary adrenal (HPA) axis. In conclusion, feeding MFGM and prebiotics to rats ameliorated the visceral pain sensitivity and cognitive impairment caused by MS. The changes to MR expression indicate that regulation of the negative feedback of the HPA axis may be partially involved. Further studies are needed to confirm this as well as elaborate on the specific mechanism of actions related to gut and brain neurochemistry.

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Supported by Science Foundation Ireland and Mead Johnson Nutrition.