肝硬化相关并发症中的肠道微生物组和代谢组特征。
Gut microbiome and metabolome signatures in liver cirrhosis-related complications.
发表日期:2024 Jul 25
作者:
Satya Priya Sharma, Haripriya Gupta, Goo-Hyun Kwon, Sang Yoon Lee, Seol Hee Song, Jeoung Su Kim, Jeong Ha Park, Min Ju Kim, Dong-Hoon Yang, Hyunjoon Park, Sung-Min Won, Jin-Ju Jeong, Ki-Kwang Oh, Jung A Eom, Kyeong Jin Lee, Sang Jun Yoon, Young Lim Ham, Gwang Ho Baik, Dong Joon Kim, Ki Tae Suk
来源:
Clinical and Molecular Hepatology
摘要:
肠道微生物群和代谢物的变化与肝硬化进展和并发症相关。然而,因果关系尚未得到全面评估。在此,我们确定了肝硬化患者的并发症依赖性肠道微生物群和代谢特征。通过 V3-V4 16S rRNA 测序对 194 份粪便样本(52 名对照者和 142 名肝硬化患者)进行了微生物组分类学分析。接下来,选择 51 个样本(17 个对照和 34 个肝硬化患者)通过气相色谱质谱法和液相色谱法结合飞行时间质谱法进行粪便代谢物分析。针对肠道微生物群、代谢物、临床参数和并发症(静脉曲张、腹水、腹膜炎、脑病、肝肾综合征、肝细胞癌和死亡)进行相关性分析。韦荣球菌、瘤胃球菌和肺炎链球菌是肝硬化-与对照组相比相关微生物群。卵形拟杆菌、共生梭菌、Emergencia timonensis、变异梭杆菌和 Hungatella_uc 与肝硬化组的并发症相关。诊断肝硬化、脑病、肝肾综合征和死亡的受试者工作特征曲线下面积 (AUROC) 分别为 0.863、0.733、0.71 和 0.69。混合微生物物种诊断肝硬化和并发症的 AUROC 分别为 0.808 和 0.847。根据代谢谱,肝硬化患者粪便代谢物增加的5种是诊断肝硬化和并发症的生物标志物(AUROC > 0.880)。临床标志物与肠道微生物群和代谢物显着相关。肝硬化依赖性肠道微生物群和代谢物呈现出独特的特征,可用作诊断肝硬化及其并发症的无创生物标志物。
Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.