Postnatal nutrition impacts the maturation of the intestinal endocrine function and the microbiota-gut-brain communications in a minipig model

Abstract

Glucagon-like peptide 1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are two main intestinal hormones regulating food behavior and metabolism. Their secretion is triggered by short chain fatty acids (SCFA) produced by the intestinal microbiota and they take a great part in the so-called microbiota-gut-brain axis. However, despite the increasing interest in nutritional programming, the way the intestinal endocrine function and the microbiota-gut-brain axis mature in infancy is still poorly documented, especially in different nutritional contexts. The aim of our study was therefore to describe this development in early infancy in the minipig as a model for humans. 36 suckling piglets (S) were euthanized 1 h after suckling at 0 (D0), 2 (D2), 5 (D5) and 10 (D10) days of age. 21 other piglets were fed from birth an infant formula containing either dairy lipids (DL) or plant lipids (PL) as fat, and euthanized 1 h after their last meal at D10. Maturation of the endocrine intestinal function was characterized by a decrease in the gene expression of the convertase 1/3 (PCSK1) converting the preproglucagon peptide in active GLP-1 as well as in the gene expressions of PYY and chromogranin A (CHGA), a global marker of enteroendocrine cells. Interestingly, this decrease took place as early as D2 in the ileon but later (D5) in the colon. The expression of the proglucagon gene (GCG) was not modified with age. The GLP-1 content of ileal and colon tissues decreased from D2 in both sites and plasma GLP-1 concentration decreased from D5. DL and PL did not modify PCSK1, CGC, PYY or CHGA gene expression at D10, but increased the SCFA receptor FFAR2 expression compared to S, as well as GLP-1 content in both the ileon and the colon, and in plasma. Interestingly, the hypothalamic expression of the GLP-1 and PYY receptors (GLP-1R and NPY2R respectively) were both increased in PL and DL piglets compared to S piglets. Endocrine intestinal function matures very quickly in infancy and in a sequential way alongside the gut, confirming that the first post-natal days constitute a critical window for health programming. Indeed, infant formula containing either dairy or plant lipids had major impacts on the natural course of this maturation, either in the gut or in the brain. Their consequences on food behavior are being evaluated and the mechanistic insights will be investigated with the characterization of the intestinal microbiota.