Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Wallenberg Laboratory, University of Gothenburg, Bruna Stråket 16, SE-413 45 Göteborg, Sweden.
Nutrients. 2020 Jul 31;12(8):2308. doi: 10.3390/nu12082308.
Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn.
血浆代谢物影响人类的一系列代谢功能，包括胰岛素敏感性 (IS)。这些血浆代谢物的一部分受肠道微生物群的影响。为了确定与 IS 相关的潜在微生物 - 代谢物途径，我们使用代谢综合征 (MetSyn) 患者外周和肝胰岛素敏感性的金标准，研究了血浆代谢物、肠道微生物群组成与 IS 之间的联系。在一项横断面研究中，对 115 名 MetSyn 参与者进行了研究，收集空腹血浆样本进行非靶向代谢组学分析，并采集粪便样本进行 16S rRNA 基因扩增子测序。进行了两步高胰岛素正葡萄糖钳夹以评估外周和肝胰岛素敏感性。整合收集的数据，并使用机器学习预测模型分析代谢物、肠道微生物群和 IS 之间的潜在相互依赖关系。血浆代谢物分别解释了外周和肝胰岛素敏感性的 13.2%和 16.7%的变异。粪便微生物群组成解释了外周胰岛素敏感性的 4.2%的变异，但与肝胰岛素敏感性无关。尽管代谢物可以部分解释 IS 的变异性，但与外周和肝胰岛素敏感性相关的顶级代谢物与肠道微生物群组成没有显著相关性（在分类学水平和 alpha 多样性上均无相关性）。然而，所有血浆代谢物都可以解释微生物 alpha 多样性（香农）的 18.5%的变异；前 20 种代谢物甚至可以解释肠道微生物 alpha 多样性的 44.5%。总之，血浆代谢物可以部分解释外周和肝胰岛素敏感性的变异性；然而，这些代谢物与肠道微生物群组成没有直接联系，突显了 MetSyn 中血浆代谢物、肠道微生物群和 IS 之间的复杂关系。
