Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, 08826, Republic of Korea.
Institute of Health and Environment, Seoul National University, Seoul, 08826, Republic of Korea.
Nat Commun. 2020 Oct 5;11(1):4982. doi: 10.1038/s41467-020-18754-5.
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.
非酒精性脂肪性肝病 (NAFLD) 与肥胖有关，但也存在于非肥胖个体中。通过 16S rRNA 测序分析了 171 名经活检证实的 NAFLD 亚洲患者和 31 名非 NAFLD 对照组的肠道微生物组谱；一个独立的西方队列用于外部验证。根据 NAFLD 的组织学谱或纤维化严重程度，将受试者分为三个亚组。在非肥胖受试者中，根据纤维化严重程度观察到微生物组多样性的显著改变，但在肥胖受试者中则没有。在非肥胖受试者中，瘤胃球菌科和韦荣氏球菌科是与纤维化严重程度相关的主要微生物群。此外，粪便胆汁酸和丙酸盐水平升高，尤其是在非肥胖且存在显著纤维化的受试者中。对与纤维化相关的瘤胃球菌科和韦荣氏球菌科物种进行宏基因组测序，并在三种小鼠 NAFLD 模型中给予四种代表性物种，以评估它们对肝损伤的影响。本研究为微生物组在肝纤维化发病机制中的作用提供了证据，尤其是在非肥胖受试者中。
