Ruminants' milk in early postnatal brain development in a pig model of the human infant : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Manawatū, New Zealand

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Given the rapid brain development in the early postnatal period and its sensitivity towards changes in the external environment like nutrition, this period is of utmost importance for determining later life health and well-being. Emerging evidence suggests a link between the triad of early life nutrition, the gut and brain axis and its potential for optimising or retrograding early postnatal brain development. In this context, human breast milk has been most studied. However, whether the development of the brain is responsive towards milk from ruminant species used to make milk formula via modulating gut-derived molecules has not been well understood. The aim, therefore, of the thesis was to evaluate the effects of milk from bovine, caprine and ovine species on circulatory blood plasma metabolites, brain tissue metabolites and brain tissue gene expression in piglets and establish associations between changes in plasma metabolite profile with neurochemical and molecular features of the brain. The hypothesis was that metabolites in the peripheral circulation would differ between different ruminant milk consumption, influencing brain metabolite and gene expression. Liquid chromatography-mass spectrometry-based metabolomics was used to profile the plasma, hippocampal, prefrontal cortex, and striatal tissue metabolite relative abundances. NanoString technology was used to evaluate the expression of genes associated with neuro- and cognitive development in the hippocampus, prefrontal cortex, and striatum tissue samples. Multi-omics data integration was used to explore the correlation between plasma and brain lipid profiles. The results showed that the relative intensity of plasma metabolites differed between bovine, caprine and ovine milk treatments, and lipid metabolites were the predominant features. The bovine group had a higher relative intensity of plasma lipids (e.g., saturated vi triglycerides, phosphatidylcholine, sphingomyelin) than the ovine and caprine milk groups, except for unsaturated triglycerides, which had a higher intensity in the ovine milk group. Metabolite profiling of brain regions indicated that the relative intensity of lipid metabolites, mainly phospholipids, changed in response to different milk treatments. Further analysis showed that in the striatum and hippocampus, the relative intensity of phospholipids in the bovine milk group was higher than in the ovine and caprine milk groups. In contrast, the relative intensity of phospholipids in the prefrontal cortex was higher in the ovine milk group than in the other milk groups. Gene expression profiling showed that the expression of genes in the striatum and hippocampus associated with neurotransmission differed between milk treatments. Both increased and decreased gene expressions were observed in response to ovine milk treatment, whereas a similar gene expression pattern was observed between the caprine and ovine milk treatments. No effect of milk treatments was observed on the prefrontal cortex gene expressions. Striatal and hippocampal lipid relative intensities showed a positive association with that of plasma lipids and the prefrontal cortex showed negative associations. Thus, this PhD research findings suggest that consuming different ruminant milk can impact early postnatal brain development by influencing the peripheral circulatory metabolites in piglets as a model of human infants
Brain, Growth, Infants, Nutrition, Animal models, Milk