Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41

Abstract

The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include shortchain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41؊/؊ and Gpr41؉/؉ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionallyraised and gnotobiotic Gpr41؊/؊ mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (؉/؉) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41؊/؊ and ؉/؉ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.host-microbial interactions ͉ energy balance ͉ enteroendocrine cells ͉ nutrient sensing ͉ polysaccharide fermentation O ur ability to effectively digest food reflects the combined activities of enzymes encoded in our primate genome and in the genomes of the trillions of microbes that reside in our distal guts. This microbial community, or microbiota, affects both sides of the energy-balance equation, influencing both the harvest of calories and the activity of host genes involved in the metabolism and storage of absorbed energy (e.g., ref.

Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway

“…Recently, the ability of the intestinal microbiome to regulate liver inflammation was established and was due in part on the ability of bacterial components in the portal blood (7). A similar effect of gut microbiome on adiposity has been demonstrated via the G protein-coupled receptor Gpr41 (28). This established that bacterial components can enter the portal circulation and regulate liver inflammation.…”

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

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Microbiota conservation and BMI signatures in adult monozygotic twins

“…Previous studies have shown that GI microbiota is host-specific and GI tract region-specific (Zoetendal et al, 2004;Rajilic-Stojanovic et al, 2009;Jalanka-Tuovinen et al, 2011), aberrant in composition and stability in patients suffering from GI disorders such as Crohn's disease (Seksik et al, 2003), and associated to host energy homeostasis (Backhed et al, 2004;Ley et al, 2006;Turnbaugh et al, 2006;Backhed et al, 2007;Samuel et al, 2008). Analysis of global fecal microbiomes introduced the concept that human GI microbiota appeared to have three distinct structural biometypes called enterotypes (Arumugam et al, 2011).…”