Department of Medicine, University of California San Diego, La Jolla, California; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany.
Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charité University Medicine, Berlin, Germany.
Gastroenterology. 2020 Nov;159(5):1839-1852. doi: 10.1053/j.gastro.2020.07.005. Epub 2020 Jul 9.
BACKGROUND & AIMS: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD.
In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles.
Patients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity.
In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.
肠道微生物组的改变与非酒精性脂肪性肝病（NAFLD）的严重程度有关。以前的研究仅专注于微生物组中的细菌；我们研究了 NAFLD 患者病毒微生物组（病毒组）的变化。
在一项前瞻性、横断面、观察性研究中，我们从 73 名 NAFLD 患者的粪便样本中提取 RNA 和 DNA 病毒样颗粒：29 名患者的 NAFLD 活动评分（NAS）为 0-4，44 名患者的 NAS 为 5-8 或肝硬化（LCI），37 名患者有 F0-F1 纤维化，36 名患者有 F2-F4 纤维化。作为对照，分析中包括 9 名无肝病的个体和 13 名轻度原发性胆汁性胆管炎患者。我们对病毒样颗粒进行了 shotgun 宏基因组测序。
与 NAS 0-4 或对照个体相比，NAS 5-8/LCI 的 NAFLD 患者肠道病毒多样性显著降低。更严重的 NAFLD 存在与噬菌体的比例显著降低有关，而与其他肠道病毒相比。使用带有留一法交叉验证的多元逻辑回归分析，我们开发了一个模型，该模型包括病毒多样性指数和简单的临床变量，该模型能够以 0.95（95%置信区间，0.91-0.99）的曲线下面积识别出 NAS 5-8/LCI 的患者，并以 0.88（95%置信区间，0.80-0.95）的曲线下面积识别出 F2-F4 纤维化的患者。添加病毒多样性数据显著改善了多元模型，包括仅基于临床参数或细菌多样性的模型。
在一项对 NAFLD 患者和对照个体粪便病毒组的研究中，我们将 NAFLD 严重程度的组织学标志物与病毒多样性和噬菌体比例的显著降低相关联。我们基于粪便病毒多样性和临床数据开发了一个模型，该模型比仅基于临床或细菌数据的模型更准确地识别出严重的 NAFLD 和纤维化患者。
