Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Metab. 2020 Nov 3;32(5):878-888.e6. doi: 10.1016/j.cmet.2020.06.005. Epub 2020 Jun 30.
Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, area under curve [AUC]). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species might offer universal utility as a non-invasive diagnostic test for cirrhosis.
肠道微生物组的失调与非酒精性脂肪性肝病 (NAFLD) 向晚期纤维化和肝硬化的进展有关。为了确定这种关联的诊断能力，我们比较了涵盖非 NAFLD 对照组、NAFLD 肝硬化患者及其一级亲属的 163 名特征明确的参与者的粪便微生物组。使用随机森林机器学习算法和差异丰度分析对 shotgun 宏基因组和非靶向代谢组学图谱进行了分析，确定了离散的宏基因组和代谢组学特征，这些特征在检测肝硬化方面同样有效（诊断准确性为 0.91，曲线下面积 [AUC]）。将宏基因组特征与年龄和血清白蛋白水平相结合，可以准确地区分来自不同地理区域的具有不同病因和遗传背景的肝硬化患者。另外纳入血清天冬氨酸氨基转移酶水平，肝硬化患者的该水平升高，可将肝硬化与纤维化的早期阶段区分开来。这些发现表明，一组核心肠道微生物物种可能作为肝硬化的非侵入性诊断测试具有普遍的适用性。
