Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention

Abstract

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Major microbiota dysbiosis in severe obesity: fate after bariatric surgery

“…MGR increased only progressively and became significant 1 year after both surgeries, concordant with previous reports: (1) 8 RYGB patients showing a non-significantly increased MGR at 1 year10; (2) increased MGR 3 months postsleeve in a cohort similar in size to ours, using shotgun sequencing12; and (3) increased richness 6 months post-RYGB using 16S-pyrosequencing 50. Noteworthy, metformin, which represents the first line of diabetes treatment23 and not a marker of T2D severity, was given at baseline to most of our patients with T2D (8/9).…”

“…It was associated with 16 MGR-related MGS contained genes encoding histidine production/degradation pathway. We found key enzymes changes in the histidine degradation pathway (KO1745, KO1712, KO1468, KO1479) that may lead to L-glutamate production, a precursor of gamma-Aminobutyric acid (GABA),12 which is linked to the downregulation of proinflammatory cytokines and inflammatory diseases 48. Glutarate was also negatively associated with MGR-related MGS and positively with HbA1C49 and could be an interesting target to further investigate for its potential link with low-grade inflammation maintenance and altered metabolism.…”

“…Compared with RYGB, AGB solely restricts food intake and induces weight loss with limited effects on digestive tract ecology or hormonal changes 8. Sleeve gastrectomy12 has been shown to significantly change gut microbiota. Post-RYGB, nine MGS significantly increased whereas two MGS decreased at M12, but they were not similar from those associated with clinical variables and MGR at baseline.…”

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

“…Although changes in fecal microbiota have been correlated with plasma metabolites in obesity and weight loss [18, 22], the interactions of microbiota and bile acids in the gut lumen with circulating metabolites and adipose tissue metabolism in humans are unknown. In the current study, we examined the effects of VLCD-induced 10% weight loss in obese women upon fecal microbiota and bile acid content and composition.…”

Functions of the Microbiota for the Physiology of Animal Metaorganisms

“…B. fragilis produces polysaccharide A, a symbiosis factor which modulates the innate immune system by inducing regulatory T cell growth and cytokine expression, ultimately protecting against colitis and inducing host-microbe symbiosis [22]. A recent study reported that the abundance of B. thetaiotaomicron is inversely correlated with obesity in Chinese subjects [23]. Importantly, in a mouse obesity model, supplementation of B. thetaiotaomicron improved metabolic parameters, thus demonstrating that B. thetaiotaomicron is functionally involved in tuning host metabolism in a beneficial manner.…”