Diener Christian, Reyes-Escogido María de Lourdes, Jimenez-Ceja Lilia M, Matus Mariana, Gomez-Navarro Claudia M, Chu Nathaniel D, Zhong Vivian, Tejero M Elizabeth, Alm Eric, Resendis-Antonio Osbaldo, Guardado-Mendoza Rodolfo
Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Gibbons Lab, Institute for Systems Biology, Seattle, WA, United States.
Front Endocrinol (Lausanne). 2021 Jan 8;11:602326. doi: 10.3389/fendo.2020.602326. eCollection 2020.
Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world's population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment-predominantly metformin-reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.
2型糖尿病(T2D)是一种全球性流行病,影响着全球超过8%的人口,是墨西哥的主要死因之一。已知饮食和生活方式会导致T2D的发病。然而,肠道微生物群在T2D进展中的作用仍不确定。微生物群组成与糖尿病之间的关联受到药物使用、饮食和肥胖的干扰。在这里,我们展示了一组405名未经治疗的墨西哥人的数据,这些人处于T2D严重程度的不同阶段。肠道细菌与200多个临床变量之间的关联揭示了一组特定的细菌属,它们是T2D患病率和风险的一致生物标志物。具体而言,血糖水平的逐渐升高、β细胞功能障碍以及测量到的T2D风险因素的积累与四个细菌属的相对丰度相关。在一个由25人组成的队列中,以二甲双胍为主的T2D治疗可靠地使微生物群恢复到正常血糖的群落状态。深入的临床特征分析使我们能够广泛控制混杂变量,表明这些微生物群模式独立于常见的T2D合并症,如肥胖或心血管疾病。我们的工作为高危人群中肠道微生物群与T2D之间的直接联系提供了首个确凿证据。特别是,我们表明T2D风险增加反映在肠道微生物群的逐渐变化中。这些与T2D相关的肠道变化是否会导致T2D的病因或其合并症仍有待观察。