Jing Zhang1, Yueqiong Ni2,3, Lingling Qian1, Qichen Fang1, Tingting Zheng2,3, Mingliang Zhang1, Qiongmei Gao1, Ying Zhang1, Jiacheng Ni1, Xuhong Hou1, Yuqian Bao1, Petia Kovatcheva‐Datchary4, Aimin Xu5,6, Huating Li1, Gianni Panagiotou5,6,2,3, Weiping Jia1
1Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China
2Systems Biology & Bioinformatics Group School of Biological Sciences The University of Hong Kong Hong Kong SAR China
3Systems Biology and Bioinformatics Unit Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute Beutenbergstrasse 11a Jena 07745 Germany
4Institute for Molecular Infection Biology, University of Wurzburg, Wurzburg, D-97080 Germany
5Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
6State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
Tóm tắt
AbstractAlthough obesity occurs in most of the patients with type 2 diabetes (T2D), a fraction of patients with T2D are underweight or have normal weight. Several studies have linked the gut microbiome to obesity and T2D, but the role of gut microbiota in lean individuals with T2D having unique clinical characteristics remains unclear. A metagenomic and targeted metabolomic analysis is conducted in 182 lean and abdominally obese individuals with and without newly diagnosed T2D. The abundance of Akkermansia muciniphila (A. muciniphila) significantly decreases in lean individuals with T2D than without T2D, but not in the comparison of obese individuals with and without T2D. Its abundance correlates inversely with serum 3β‐chenodeoxycholic acid (βCDCA) levels and positively with insulin secretion and fibroblast growth factor 15/19 (FGF15/19) concentrations. The supplementation with A. muciniphila is sufficient to protect mice against high sucrose‐induced impairment of glucose intolerance by decreasing βCDCA and increasing insulin secretion and FGF15/19. Furthermore, βCDCA inhibits insulin secretion and FGF15/19 expression. These findings suggest that decreased abundance of A. muciniphila is linked to the impairment of insulin secretion and glucose homeostasis in lean T2D, paving the way for new therapeutic options for the prevention or treatment of diabetes.
