Effects of a sugar-rich diet combined with Roux-en-Y bariatric surgery on the metabolism, gut microbiota and brain activity in rats

Roux-en-Y gastric bypass (RYGB) is an invasive bariatric surgery which has been proven successful in weight loss and improvement or resolution of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for more sufficient therapeutic approaches. Here, we investigated systemic RYGB surgery effects in a liquid sucrose diet induced rat obesity model. RYGB or a control sham surgery was applied after an eight-week high liquid sucrose diet in rats. After recovery the RYGB, sham pair-fed and sham ad libitum group further continued the diet. Metabolomics, microbiome, brain imaging, immunohistology and hepatic lipid analysis revealed notable alterations in microbiota composition, inflammatory markers, feces, liver and plasma metabolites as well as neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, suggesting altered enteric nervous system (ENS) and gut signaling. Favorable plasma insulin, c-reactive protein (CRP), serine, glycine and 3-hydroxybutyrate profiles suggested reverted obesity risk. Liquid sucrose diet and caloric restriction mainly manifested in hepatic fatty acid changes. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.