The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.

由于已知抗糖尿病治疗的混杂效应，肠道微生物群与 2 型糖尿病 (T2D) 之间的联系值得进一步研究。在这里，我们在一个发现 (n = 1,011) 和验证 (n = 484) 队列中分析了肠道微生物群，该队列包括未接受过糖尿病治疗的瑞典受试者，并按血糖状态分组。我们观察到，葡萄糖耐量受损、葡萄糖耐受不良和 T2D 组的整体肠道微生物群组成发生了改变，但空腹血糖受损的组没有发生改变。此外，在糖尿病前期和 T2D 组中，几种丁酸生产者的丰度和丁酸生产的功能潜力都降低了。多变量分析和机器学习微生物组模型表明，胰岛素抵抗与微生物变异密切相关。所以，