Shaping the Metabolism of Intestinal Bacteroides Population through Diet to Improve Human Health

The human intestinal microbiota is dominated by five phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. In adults, more than 80% of the species belong to just two phyla, Firmicutes and Bacteroidetes. Short chain fatty acids (SCFA) are catabolic end-products from intestinal microbial fermentation. Acetate, propionate and butyrate are the most abundant (Ríos-Covián et al., 2016a) whilst branched chain fatty acids (BCFA; isobutyrate, valerate, and isovalerate), the organic acids lactate, succinate, formate, and gases, can be also formed. In humans, the main fermentable sources of SCFA are undigested dietary polysaccharides; amino acids and proteins may constitute additional substrates for colonic fermentation, whereas host-derived glycoproteins contribute to a limited extent. BCFA can be formed at considerably lower proportions than SCFA from branched-chain amino acids (BCAA; valine, leucine, and isoleucine). Threonine renders propionate and butyrate, whereas glutamate, histidine, lysine, arginine, and alanine give rise to acetate and butyrate formation; additionally, the intestinal microbiota contributes to the production of amino acids available to the host through de novo biosynthesis (Neis et al., 2015). Moreover, metabolic cross-feeding, that is the utilization of end products from the carbohydrate catabolism of a given microorganism by another one, strongly influences the final balance of intestinal SCFA. It occurs mainly for the formation of butyrate from acetate or lactate, is considerably lower for butyrate conversion to propionate, and very scarce between propionate and acetate (Den Besten et al., 2013). Intestinal SCFA can incorporate into the enterohepatic circulation, being metabolized in the liver and reaching other extra-intestinal locations (Den Besten et al., 2014). Increasing evidence supports a regulatory role for SCFA in glucose homeostasis and lipid metabolism, in which intestinal SCFA ligands FFAR2 and FFAR3 and the glucagon-like peptide are involved. In the liver propionate is gluconeogenic whereas acetate and butyrate are lipogenic. Recent studies evidence that propionate and butyrate activate the intestinal gluconeogenesis (De Vadder et al., 2014), the glucose synthesized serving as a homeostatic signal in the portal system, to control hepatic gluconeogenesis (causal factor of insulin resistance and type 2 diabetes) and improving whole-body glucose homeostasis. Moreover, propionate flux through the liver reduces visceral and liver fat by decreasing intrahepatic triglycerides (Chambers et al., 2015). Propionate inhibits hepatic lipogenesis and cholesterogenesis promoted by acetate (Demigne et al., 1995) whereas propionate and butyrate inhibit lipolysis and lipogenesis and increase the incorporation of glucose mediated by insulin into the adipose tissue (Heimann et al., 2015). These observations prompt to …