Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD.
Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD.
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DOI：
10.1038/s41467-020-18754-5
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发表时间：
2020-10-05
影响因子：
16.6
通讯作者：
Ko G
中科院分区：
文献类型：
--
作者：
Lee G;You HJ;Bajaj JS;Joo SK;Yu J;Park S;Kang H;Park JH;Kim JH;Lee DH;Lee S;Kim W;Ko G
非酒精性脂肪性肝病(NAFLD)与肥胖有关，但也可在非肥胖者中发现。应用16S rRNA测序技术分析了171例经活检证实为NAFLD的亚洲患者和31例非NAFLD对照患者的肠道微生物组特征；一个独立的西方队列用于外部验证。受试者根据NAFLD的组织学谱或纤维化严重程度被分为三个亚组。在非肥胖但不肥胖的受试者中，根据纤维化的严重程度观察到微生物组多样性的显著变化。在非肥胖者中，瘤胃球菌科和韦龙菌科是与纤维化严重程度相关的主要微生物区系。此外，大便胆汁酸和丙酸升高，特别是在有显著纤维化的非肥胖者。与肝纤维化相关的瘤胃球菌科和韦龙球菌科的物种进行了元基因组测序，并在三个小鼠NAFLD模型中对四个代表性物种进行了研究，以评估它们对肝脏损伤的影响。这项研究为微生物群在肝纤维化发病机制中的作用提供了证据，特别是在非肥胖者中。非酒精性脂肪性肝病(NAFLD)与肥胖有关，但也可在非肥胖者中发现。在这里，使用经活检证实的NAFLD队列进行的肠道微生物组分析显示，微生物组代谢产物的明显特征与非肥胖NAFLD患者的显著纤维化有关。
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects. Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.
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