Non-alcoholic fatty liver disease (NAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants, obesity and diabetes, we characterized 56 heterogeneous NAFLD patients by generating multi-omics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. We explored the dysbiosis in the oral and gut microbiome and revealed host-microbiome interactions based on global metabolic and inflammatory processes. We integrated this multi-omics data using the biological network and identified HS’s key features using multi-omics data. We finally predicted HS using these key features and validated our findings in a validation dataset, where we characterized 22 subjects with varying degree of HS.

中文翻译：

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多组学分析揭示微生物群对肝脂肪变性宿主代谢的影响

非酒精性脂肪肝 (NAFLD) 是一种复杂的疾病，涉及多种生物过程的改变，这些过程受肥胖、遗传背景和环境因素（包括微生物组）之间的相互作用的调节。为了通过排除包括遗传变异、肥胖和糖尿病在内的关键混杂因素来破译肝脂肪变性 (HS) 发病机制，我们通过生成多组学数据（包括口腔和肠道宏基因组学以及血浆代谢组学和炎症蛋白质组学数据）来表征 56 名异质 NAFLD 患者。我们探索了口腔和肠道微生物群中的生态失调，并揭示了基于整体代谢和炎症过程的宿主-微生物群相互作用。我们使用生物网络整合了这些多组学数据，并使用多组学数据确定了 HS 的关键特征。