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

Abstract

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.

Microbiome: A complicated relationship status

“…Bolstering the observations in humans, similar changes have been found in the microbiota of rats and mice that undergo gastric bypass operations. In fact, if gut microbes from a post-surgery mouse are transferred to a mouse lacking gut microbes, the recipient mouse loses weight 13 .…”

Biotic interactions and temporal dynamics of the human gastrointestinal microbiota

“…The relevant taxonomic scale of observation is contingent on the type of question, as effects of the GI microbiota on the host have been linked to interactions on different taxonomic levels, for example, phylum (Turnbaugh et al, 2009), genera (Liou et al, 2013) and species (Mazmanian et al, 2008). In vitro studies of GI bacteria have even shown that strain-level dynamics can be determined by interactions with very distantly related taxa (de Muinck et al, 2013).…”

Does gastric bypass surgery change body weight set point?

“…The gut microbiome changes after gastric bypass surgery in humans, [66][67][68] rats 69 and mice, 70 and a recent transplant study in mice suggests that the changes in gut microbiome are responsible for at least some effects on body weight. 70 The signaling pathways leading from the microbiota in the intestinal lumen to reduced body weight are not known (Figure 3).…”

“…70 The signaling pathways leading from the microbiota in the intestinal lumen to reduced body weight are not known (Figure 3). One possibility is that microbiota-induced effects on intestinal barrier function reverse obesity-associated endotoxemia and inflammation.…”