Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment

Abstract

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

“…Abundant evidence has demonstrated the important roles of bile acids in glucose homeostasis . Total plasma bile acid concentrations are higher in obese and T2D subjects than in healthy controls, whereas bile acid pools are also regulated by glucose‐lowering drugs such as metformin and acarbose . In the present study, we showed that saxagliptin, a DPP‐4 inhibitor, significantly increased serum concentrations of CA, GCA, GCDCA, GDCA, and GUDCA in both NW and OW/OB T2D patients, and with CDCA and DCA levels also increasing in the OW/OB group.…”

“…Human studies have demonstrated that the bile acid composition in diabetic or obese patients differs from that in normal populations . Moreover, metabolic surgeries and glucose‐lowering drugs, such as metformin and acarbose, have been reported to regulate the bile acid pool contributing to glucose control . This evidence suggests that bile acids may be involved in the pathophysiological process of metabolic diseases.…”

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

“…172,173 Metformin reduced the abundance of B. fragilis in patients with type 2 diabetes and increased the concentration of bile acid glycoursodeoxycholic acid. 175 174 Similarly, acarbose is recommended for the treatment of type 2 diabetes.…”

“…Treatment with acarbose increased the relative abundances of Lactobacillus and Bifidobacterium and reduced Bacteroides, thereby changing bile acid metabolism. 175…”

M2IA: a Web Server for Microbiome and Metabolome Integrative Analysis

“…Thus, the microbiota-metabolites interactions are important to maintain the host health and wellbeing. Integrative data analysis of gut microbiome and metabolome can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases (e.g., autoimmune diseases, inflammatory bowel disease [5] , cancers [6] , type 2 diabetes and obesity [7] , cardiovascular disorders, and non-alcoholic fatty liver disease [8] ), and provide potential diagnostic and therapeutic targets [9] .…”