Shanghai 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.
Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Beutenbergstrasse 11a, Jena, 07745, Germany.
Adv Sci (Weinh). 2021 Aug;8(16):e2100536. doi: 10.1002/advs.202100536. Epub 2021 Jun 4.
Although 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.
虽然 2 型糖尿病（T2D）患者大多肥胖，但也有一部分 T2D 患者体重过轻或体重正常。已有多项研究将肠道微生物组与肥胖和 T2D 联系起来，但肠道微生物群在具有独特临床特征的瘦型 T2D 患者中的作用仍不清楚。对 182 名瘦型和腹部肥胖的个体（无论是否患有新诊断的 T2D）进行了宏基因组和靶向代谢组学分析。与无 T2D 的个体相比，患有 T2D 的瘦型个体中阿克曼氏菌（A. muciniphila）的丰度显著降低，但在肥胖个体中则没有这种差异。其丰度与血清 3β-鹅脱氧胆酸（βCDCA）水平呈负相关，与胰岛素分泌和成纤维细胞生长因子 15/19（FGF15/19）浓度呈正相关。补充阿克曼氏菌足以通过降低βCDCA 并增加胰岛素分泌和 FGF15/19 来保护小鼠免受高蔗糖诱导的葡萄糖耐量受损。此外，βCDCA 抑制胰岛素分泌和 FGF15/19 的表达。这些发现表明，A. muciniphila 丰度的降低与瘦型 T2D 患者胰岛素分泌和葡萄糖稳态的损害有关，为预防或治疗糖尿病开辟了新的治疗选择。
