College of Pharmacy, Oregon State University, Corvallis, OR, USA.
Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Nat Commun. 2021 Jan 4;12(1):101. doi: 10.1038/s41467-020-20313-x.
Western diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes (T2D) with gut microbiota playing an important role in modulating effects of the diet. Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism. Interrogation of this network pointed to taxa with potential beneficial or harmful effects on host's metabolism. We then validate the functional role of the predicted bacteria in regulating metabolism and show that they act via different host pathways. Our gene expression and electron microscopy studies show that two species from Lactobacillus genus act upon mitochondria in the liver leading to the improvement of lipid metabolism. Metabolomics analyses revealed that reduced glutathione may mediate these effects. Our study identifies potential probiotic strains for T2D and provides important insights into mechanisms of their action.
西方饮食（WD）是代谢性疾病（包括 2 型糖尿病（T2D））的主要罪魁祸首之一，肠道微生物群在调节饮食的影响方面起着重要作用。在此，我们使用数据驱动的方法（跨王国网络分析）来模拟 WD 下的宿主-微生物组相互作用，以推断微生物组的哪些成员有助于改变宿主的新陈代谢。对该网络的查询指出了对宿主代谢具有潜在有益或有害影响的分类群。然后，我们验证了预测细菌在调节代谢中的功能作用，并表明它们通过不同的宿主途径发挥作用。我们的基因表达和电子显微镜研究表明，来自乳杆菌属的两种物种作用于肝脏中的线粒体，从而改善脂质代谢。代谢组学分析表明，还原型谷胱甘肽可能介导这些作用。我们的研究确定了 T2D 的潜在益生菌菌株，并为它们的作用机制提供了重要的见解。
