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

Yuchao Gu ,Jialin Yang,Xinjie Zhao,Yongde Peng,Guowang Xu,Dongya Zhang,Karsten Kristiansen,Junhua Li,Xiaoqiang Xu,Hongmei Zhang,Weiqiong Gu,Yifei Zhang,Jing Ma,Jing Hong ,Xiaoyan Xie,Xun Xu,Huanming Yang,Qiang Feng,Wei Liu,Lise Madsen,Qing Su,Zhong Huang ,Huihua Xia,Xiaokai Wang,Guang Ning,Huahui Ren,Yufang Bi,Fang Li,Ruixin Liu,Xiaoling Wang,Weiqing Wang

doi:10.1038/s41467-017-01682-2

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.

Highlights

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health
This study compared the effects of two antidiabetic drugs on the gut microbiota, plasma BAs and their relations with clinical outcomes in a clinical trial-based cohort
A key finding of this study is that the baseline composition of the gut microbiota may be used for stratification of patients prior to initiation of treatment

Summary

Results

Baseline characteristics of patients and clinical outcomes. WC, waist circumference; WHR, waist–hip circumference ratio; HbA1c, glycated haemoglobin; FPG, fasting plasma glucose; PPG, postprandial plasma glucose; AUC, area under the curve; HOMA-IR, homeostasis model assessment of insulin resistance; LDL, low-density lipoprotein; HDL, high-density lipoprotein; FLI, fatty liver index: FLI = (e0.953 × loge [TG] + 0.139 × BMI + 0.718 × loge[γGT] + 0.053 × WC − 15.745)/(1 + e0.953 × loge [TG] + 0.139 × BMI + 0.718 × loge [γGT] + 0.053 × WC − 15.745) × 100. At the end of the 3-month treatment, the reductions in HbA1c Wilcoxon rank-sum test, P < 0.01 between baseline and treatlevels, and fasting blood glucose (FBG) and postprandial blood ment, Table 1), and both arms reached the targeted level of glucose (PBG) levels were significant in both groups

11 Acarbose pre Acarbose post

Discussion

Methods