Background The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity. Objective To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues. Design Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose). Results Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes. Conclusion These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.Cite Now Data are available upon reasonable request.

中文翻译：

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多项研究中肠-肝脏-脂肪轴的多组学揭示了肠道微生物群与全身葡萄糖代谢的抗病毒反应之间的一致联系


背景 微生物群正在成为胰岛素抵抗和肥胖易感性的关键因素。目的 了解肠道菌群与多组织中胰岛素敏感性之间的相互作用。设计 跨 6 项研究的综合多组学和多组织方法，将正常血糖钳夹测量（用于 6 项研究中的 4 项）与葡萄糖代谢和胰岛素抵抗的其他测量（糖化血红蛋白 （HbA1c） 和空腹血糖）相结合。结果 在 4 项研究中，来自变形菌门的几个属和种始终与胰岛素敏感性呈负相关 （ADIPOINST，n=15;IRONMET，n=121，FLORINASH，n=67 和 FLOROMIDIA，n=24）。空肠、回肠和结肠的转录组学分析显示 T 细胞相关特征与胰岛素敏感性呈正相关。回肠和结肠中的变形菌门与 HbA1c 呈正相关，但与 T 细胞数量呈负相关。空肠脱氧胆酸与胰岛素敏感性呈负相关。皮下脂肪组织 （ADIPOMIT，n=740） 和内脏脂肪组织 （VAT） （ADIPOINST，n=29） 的转录组学揭示了分别与 HbA1c 和胰岛素敏感性相关的 T 细胞相关特征。VAT 变形菌门与胰岛素敏感性呈负相关。ADIPOINST 和 FLORINASH 研究中的多组学和多组织整合将粪便变形菌门与空肠和肝脏脱氧胆酸以及参与肌动蛋白细胞骨架、胰岛素和 T 细胞信号传导的空肠、VAT 和肝脏转录组特征联系起来。空腹血糖始终与干扰素诱导的基因和肠道和 VAT 中的抗病毒反应有关。 对黑腹果蝇的研究验证了这些与人类胰岛素敏感性相关的变化。结论这些数据为微生物组-肠道-脂肪-肝脏轴及其对全身胰岛素作用的影响提供了全面的见解，表明了潜在的治疗靶点。应合理要求提供 Cite Now 数据。