Gastric bypass surgery in a rat model alters the community structure and functional composition of the intestinal microbiota independently of weight loss

Abstract

Background: Roux-en-Y gastric bypass (RYGB) surgery is a last-resort treatment to induce substantial and sustained weight loss in cases of severe obesity. This anatomical rearrangement affects the intestinal microbiota, but so far, little information is available on how it interferes with microbial functionality and microbial-host interactions independently of weight loss. Methods: A rat model was employed where the RYGB-surgery cohort is compared to sham-operated controls which were kept at a matched body weight by food restriction. We investigated the microbial taxonomy and functional activity using 16S rRNA amplicon gene sequencing, metaproteomics, and metabolomics on samples collected from theileum, the cecum, and the colon, and separately analysed the lumen and mucus-associated microbiota. Results: Altered gut architecture in RYGB increased the relative occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria, while in general, Firmicutes were decreased although Streptococcaceae and Clostridium perfringens were observed at relative higher abundances independent of weight loss. A decrease of conjugated and secondary bile acids was observed in the RYGB-gut lumen. The arginine biosynthesis pathway in the microbiota was altered, as indicated by the changes in the abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. Conclusion: The anatomical rearrangement in RYGB affects microbiota composition and functionality as well as changes in amino acid and bile acid metabolism independently of weight loss. The shift in the taxonomic structure of the microbiota after RYGB may be mediated by the resulting change in the composition of the bile acid pool in the gut and by changes in the composition of nutrients in the gut.

Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR

“…However, previous findings from diet-induced obese mice and rats, as well as genetically obese and insulin-resistant ZDF rats, have established that reduced intestinal permeability/attenuated endotoxemia following RYGB occur independently of food/high-fat diet restriction and weight loss ( Guo et al., 2019 ; Steensels et al., 2017 ; Wang et al., 2019a ). Additionally, we previously found that colonic CA and CDCA concentrations are twice as high in RYGB-operated, diet-induced obese rats compared with body weight-matched, sham-operated counterparts ( Haange et al., 2020 ), further supporting the view that gastrointestinal reconfiguration-induced changes in bile flow and bile acid metabolizing intestinal microbiota per se , contribute to increased colonic FXR activation and stabilization of the IEB ( Figure 6 ). This is also supported by the finding that the jejunal contents of RYGB-operated rats stabilized barrier function in Caco-2 cells independently of FXR, since bile flow is redirected away from the upper/mid jejunum post-operatively.…”

“…This revealed region-specific, barrier-stabilizing effects for the intestinal contents of RYGB-operated compared with sham-operated rats, possibly mediated by the action of various host- and/or microbiota-generated soluble factors. These potentially include, but are not limited to, hepatocyte-derived conjugated primary bile acids, that may become concentrated in the duodenum following RYGB due to redirection of ingested food passage to the mid-jejunum ( Ise et al., 2019 ), as well as microbiota-derived metabolites such as indole-3-propionic acid ( Jennis et al., 2018 ; Natividad et al., 2018 ), secondary bile acids ( Haange et al., 2020 ; Lajczak-McGinley et al., 2020 ), taurine ( Ahmadi et al., 2020 ; Wang et al., 2019a ), and the short chain fatty acid propionate ( Liou et al., 2013 ; Tong et al., 2016 ). Future metabolomics studies are required to confirm this, and to potentially discover novel soluble factors that stabilize the IEB.…”

Microbial Adaptation Due to Gastric Bypass Surgery: The Nutritional Impact

“…For this purpose, mouse models, using calorie restriction or sham-operated pair-fed individuals as diet-matched controls could be a helpful tool. There is some evidence from experimental studies on rats, which indicates that the observed effects on gut microbiota composition and diversity after RYGB surgery are associated with surgery itself [84,85]. Guo et al found similar glucose improvement and increased gut microbiota diversity 10 weeks after RYGB and SG surgery compared with the sham-operated groups (pair-fed as RYGB or fed ad litidum).…”

Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

“…[ 55 , 57 ] Many studies reported that intestinal rearrangement after RYGB is a vital factor for the gut microbial changes. [ 59 , 60 , 64 ] Nevertheless, proton pump inhibitor therapy during the first 3 months after surgery and antibiotics used during the peri-operative period can also influence the gut microbiota, which clinicians should be aware of. Does the changed gut microbiota have some effects on metabolic alterations after RYGB?…”