Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity

Abstract

The gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels of circulating branched-chain amino acids (BCAA) and their cognate a-ketoacids (BCKA) were significantly correlated with the body weight in humans and mice and that BCAA catabolic defects in BAT were associated with obesity in diet-induced obesity (DIO) mice. Pharmacological systemic enhancement of BCAA catabolic activity reduced plasma BCAA and BCKA levels and protected against obesity; these effects were reduced in BATectomized mice. DIO mice gavaged with Bacteroides dorei and Bacteroides vulgatus exhibited improved BAT BCAA catabolism and attenuated body weight gain, which were not observed in BATectomized DIO mice. Our data have highlighted a possible link between the gut microbiota and BAT BCAA catabolism and suggest that Bacteroides probiotics could be used for treating obesity.

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

“…alters gut microbiota composition and reduces the levels of BCAA and BCKA in BAT, proving the beneficial effect of Bacteroides spp. in the catabolism of BCAA in BAT ( 31 ). Many studies that are targeted at microbiota intervention have suggested that regulating the BCAAs can be achieved by changing the gut microbiota, thus showing a promising therapeutic prospect.…”

The Emerging Role of Branched-Chain Amino Acids in Liver Diseases

“…In relation to BCAAs’ metabolism, other members of the gut microbiota, Bacteroides vulgatus and Bacteroides dorei, were reported to improve BCAAs’ catabolism in brown adipose tissue and improve systemic glucose tolerance and insulin sensitivity in high-fat diet-induced obesity mice [ 99 ]. These species were previously found to be downregulated in T2D individuals, and their high abundance in obese mice was found to confer protective effects, i.e., in preventing the mice from developing T2D and NAFLD [ 100 ].…”

Determination of the Nutritional Value of Diet Containing Bacillus subtilis Hydrolyzed Feather Meal in Adult Dogs

“…However, the most observed genera in the feces of dogs fed 9.09% HFMBs or 9.09% HFMT were Bacteroides , Cetobacterium , and Fusobacterium . Species from the Bacteroides genus generally inhabit the colon, are chemoheterotrophic and promotes the catabolism of branched chain amino acids [ 56 ]. Amino acid metabolism by gut microbiota results in a complex mixture of metabolic end products including among others ammonia, short-chain and branched-chain fatty acids, which are important bacterial metabolites influencing epithelial physiology and modulating the mucosal immune system of the host [ 57 ].…”