Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity

Alterations in the gastrointestinal microbiota caused by gastric bypass surgery are sufficient to trigger decreased body weight and adiposity in germ-free mouse recipients. Getting By(pass) with Help from Our Little Friends One of the most durably effective treatments for severe obesity is gastric bypass surgery. Despite its powerful effect on weight loss and remission of diabetes, the cost and associated risk of this procedure prevents its application to a large population of obese patients, prompting a search for less invasive treatments. The population structure of the trillions of microorganisms that reside in the human gut is markedly altered after gastric bypass, but the functional importance of these changes is unknown. In a new study, Liou et al. use a mouse model of gastric bypass surgery to characterize changes in the gut microbiota, both temporally and along the length of the gastrointestinal tract. Gastric bypass induced substantial, rapid, and sustained changes to the gut microbial communities that were independent of both diet and the weight loss associated with this procedure. The observed changes in this mouse model were similar to those previously observed in human gastric bypass patients. Transfer of the surgically altered microbial community to nonoperated, germ-free mice resulted in weight loss and decreased body fat. Gastric bypass was also associated with changes in the production of short-chain fatty acids, changes that were conveyed to the previously germ-free mice that received the microbiota from these operated animals. These observations demonstrate that specific alterations in the gut microbiota contribute to the beneficial effects of bariatric surgery on energy balance and obesity. They suggest new approaches to the treatment of obesity and related metabolic diseases that harness the ability of the gut microbiota to influence host metabolic physiology. Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.