美国加州大学Rohit Loomba和索尔克生物研究所Ronald M. Evans研究组合作取得进展。他们揭示了可以预测肝硬化的通用肠道微生物组特征。这一研究成果于2020年6月30日在线发表在《细胞-代谢》上。

为了确定肝硬化诊断与肠道微生物的相关程度，研究人员比较了包括非-非酒精性脂肪性肝（NAFLD）对照、NAFLD肝硬化患者及其直系亲属在内的163名特征明确参与者的粪便微生物组。通过使用随机森林机器学习算法结合鸟枪法宏基因组学和非目标代谢组学谱的差异丰度分析，研究人员发现离散的宏基因组学和代谢组学特征在检测肝硬化方面同样有效（诊断准确度为0.91，曲线下面积[AUC]）。

将宏基因组学特征与年龄和血清白蛋白水平相结合，可以准确地区分在地理上分离区域病因和遗传上不同人群的肝硬化。肝硬化患者的血清天冬氨酸转氨酶水平增加，这可以区分肝硬化和早期纤维化。这些发现表明肠道微生物组种类可能为肝硬化的非侵入性诊断提供便利。

据悉，肠道微生物组紊乱与NAFLD向晚期纤维化和肝硬化的发展有关。

附：英文原文

Title: A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis

Author: Tae Gyu Oh, Susy M. Kim, Cyrielle Caussy, Ting Fu, Jian Guo, Shirin Bassirian, Seema Singh, Egbert V. Madamba, Ricki Bettencourt, Lisa Richards, Manuela Raffatellu, Pieter C. Dorrestein, Ruth T. Yu, Annette R. Atkins, Tao Huan, David A. Brenner, Claude B. Sirlin, Rob Knight, Michael Downes, Ronald M. Evans, Rohit Loomba

Issue&Volume: 2020-06-30

Abstract: Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholicfatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnosticcapacity of this association, we compared stool microbiomes across 163 well-characterizedparticipants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and theirfirst-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomicprofiles by using the random forest machine learning algorithm and differential abundanceanalysis identified discrete metagenomic and metabolomic signatures that were similarlyeffective in detecting cirrhosis (diagnostic accuracy 0.91, area under curve [AUC]).Combining the metagenomic signature with age and serum albumin levels accurately distinguishedcirrhosis in etiologically and genetically distinct cohorts from geographically separatedregions. Additional inclusion of serum aspartate aminotransferase levels, which areincreased in cirrhosis patients, enabled discrimination of cirrhosis from earlierstages of fibrosis. These findings demonstrate that a core set of gut microbiome speciesmight offer universal utility as a non-invasive diagnostic test for cirrhosis.

DOI: 10.1016/j.cmet.2020.06.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30306-5