Small intestinal physiology relevant to bariatric and metabolic endoscopic therapies: Incretins, bile acid signaling, and gut microbiome

Abstract

Incretins, bile acids and the gut microbiome are involved in the pathophysiology of obesity and type 2 diabetes. The incretins glucagon-like peptide-1 and glucose-dependent-insulinetrophic polypeptide, both influence beta-cell function, insulin and glucose sensitivity, and food intake. Studies have shown that concentrations of both incretins change after bariatric surgery and nowadays glucagon-like peptide-1 agonists are administered as glucose and body weight regulating agents. Bile acids also play an important role in glycemic and metabolic regulation via multiple signaling pathways. After bariatric surgical interventions increase in bile acid concentrations have been observed combined with improvement of metabolic health. It is not clear though, whether this is a direct effect of the altered concentration of bile acids or an epiphenomenon. In addition, alterations in the microbiome are seen in patients with type 2 diabetes and people with obesity. The gut microbiome, probably together with incretins and bile acids, is essential in digestion and nutrient metabolism. After bariatric procedures several alterations in bacterial abundance have been demonstrated with specific bacterial species having different effects on glycemic and metabolic conditions

A Changed Gut Microbiota Diversity Is Associated With Metabolic Improvements After Duodenal Mucosal Resurfacing With Glucagon-Like-Peptide-1 Receptor Agonist in Type 2 Diabetes in a Pilot Study

“…This means that improvement in glycaemic control was correlated with increased gut microbiota diversity in our patients with T2DM. These findings are supported by a recently published systematic review of other metabolic procedures, reporting increased gut microbiota diversity in patients with metabolic improvements following endoscopic and surgical metabolic procedures across several studies (3). However, we did not find increased diversity of the gut microbiota in our complete (n=16) population after the intervention compared to baseline.…”

Duodenal mucosal resurfacing with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent type 2 diabetes

“…Mechanism of action behind these glycemic and metabolic improvements after bariatric surgery and endoscopic duodenal interventions such as DMR and EndoBarrier has not been fully elucidated. However, some of the mechanisms are linked to endocrine actions of bile acids ( 14 ).…”

Alternative treatments for type 2 diabetes and associated metabolic diseases: medical therapy or endoscopic duodenal mucosal remodelling?

“…An interaction between incretin and bile acids (BA) driven by modulation of the farnesoid X nuclear receptor has also been described, 37 and in line with the preliminary results from the INSPIRE study suggests that BAs may mediate the postablation effect. We observed an increase in postprandial unconjugated and secondary BA levels following DMR.…”