Investigation of the involvement of the microbiota-intestine-brain axis in the etiology of endocrine pancreatic dysfunction in mice subjected to protein malnutrition

Abstract

The Gastrointestinal Tract (GT) provides information to the Central Nervous System (CNS) about the nutritional status of the individual in partly through the gut-brain axis. The intestinal microbiota also contribute to this flux of information through neurohormonal mechanisms between GT and CNS, constituting the Microbiota-Gut-Brain (MGB) axis. The putative mediators involved in this processes are Short Chain Fatty Acids (SCFAs), produced by bacterial fermentation, which act on the MGB axis via regulation of GT afferents to the CNS, or through stimulation of enteroendocrine cells that release tyrosine-tyrosine peptide (PYY)- or glucagon-like peptide (GLP)-1. Remarkably, MGB axis efferents regulate GT function and other tissues in the organism, among them is important to emphaticize the increase in insulin secretion through the activation of the parasympathetic nervous system to the pancreas. Indirectly, gut microbiota also regulates ²-cell function through SCFAs that stimulate PYY and GLP-1 secretion from the gut. Therefore, the microbiome participates of various physiological regulatory mechanisms to ensure homeostasis, and dysbiosis may lead to neuroendocrine and metabolic impairments. Our laboratory showed that protein restriction in rodents lead to reductions in insulin secretion and ²-cell mass; in contrast this malnutrition increase glucagon secretion and ±-cell mass. Therefore, it is possible that endocrine pancreatic dysfunction in malnourished mice may occur due to a gut dysbiosis, which would modify the intestinal and circulating levels of SCFAs that directly or indirectly should impair the MGB communication with the endocrine pancreas. Thus, this study by addressing the MGB axis and its effects on endocrine pancreas, for the first time will demonstrate how the gut microbiota in protein-undernourished mice could impair ²-cell morphofunction, contributing to the physiopathological characterization and the establishment of new therapeutic strategies for this type of malnutrition. (AU)