Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations.

Laimdota Zizmare,Ketki Mulay,Ralf Krüger,Isabelle Mack,Christoph Trautwein,Sandrine Louis,Sabrina Buss,Manuel Rodriguez Gomez,Christina N Boyle,Yvonne Ritze,Kristina Herfert,Laura Kuebler,Lara Steinhauer

doi:10.3390/ijms23031126

Abstract

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. 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.

Highlights

Obesity is a metabolic and inflammatory health condition characterized by excess accumulation of body fat, which increases the risk of developing an unbalanced, unresolved metabolic inflammation within adipose tissue and in metabolic organs such as the liver, pancreas and, brain [1,2]
Liquid Sucrose-Induced Obesity Is Reverted by Roux-en-Y gastric bypass (RYGB) Surgery
Increased lipopolysaccharide-binding protein (LBP) in plasma is a known marker for inflammation [67], we did not observe any other signs for an upregulated inflammatory response in the RYGB group compared to the sham

Summary

Introduction

Obesity is a metabolic and inflammatory health condition characterized by excess accumulation of body fat, which increases the risk of developing an unbalanced, unresolved metabolic inflammation within adipose tissue and in metabolic organs such as the liver, pancreas and, brain [1,2]. A chronic, whole-body meta-inflammatory state during obesity can further lead to cardiovascular disease, type 2 diabetes, dysregulation of the immune system, and impaired cognitive and mental capabilities [3,4,5,6,7,8]. Prolonged intake of high sugar foods, a principal component of the Western diet, promoted excess energy intake and gain of body weight [9]. Obesity and type 2 diabetes are important risk factors in the pathogenesis of cognitive dysfunction [11,12,13]. A Western diet is associated with reduced expression of brain-derived neurotrophic factors, elevated levels of oxidative stress, and pro-inflammatory processes in neurons, and affects the whole-body immune response [14]

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Results

Conclusion