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浙大发现与肝硬化相关的肠道菌群遗传特征

摘要 : 近日,浙江大学医学院附属第一医院传染病诊治国家重点实验室、感染性疾病诊治协同创新中心主任李兰娟院士及其科研团队,找到了汉族人和肝硬化相关的肠道菌群的遗传特征,为检测晚期肝疾病提供了方法。该研究成果于7月24日在学术期刊《自然》在线发表。

目前,部分病毒性肝炎及脂肪性、酒精性、药物性、免疫性肝病患者会经历肝炎、肝硬化、肝癌“三部曲”。尽管有些研究表明,肠道微生物的改变在终末期肝硬化并发症中起重要作用,但一直缺乏肠道菌群和肝脏病变的确切关联证据。

李兰娟院士及其科研团队通过收集181个来自于中国人肠道菌群的样本,其中包括98个中国肝硬化患者及83个健康中国志愿者的粪便样本,用宏基因组学的研究方法,开展了肝硬化肠道菌群的深度测序及关联分析研究,从中获得269万个非冗余的人体肠道微生物菌群的基因集,建立了世界上首个肝病肠道菌群基因集,其中36.1%的基因为首次发现。

据科研人员介绍,他们首次发现肝硬化患者口腔菌侵入到肠道,其中增多的菌群包括如弯曲杆菌和嗜血杆菌等病原体。这些可能是通过受污染的食物由口腔入侵到肠道,而健康人中没有此现象,这将对肝硬化发生、发展产生重要影响。此研究是首次开展肝硬化肠道菌群微生物的关联分析研究,从肠道菌群发生紊乱的角度揭示肝硬化发生发展的机制,确定了健康志愿者和肝硬化患者相关的肠道菌群的群落结构及功能。

科研人员还发现了15个高特异性和灵敏性的微生物基因,建立了预测疾病的模型,不仅有助于肝硬化诊断,还能用于肝硬化疗效的评估。

原文摘要:

Alterations of the human gut microbiome in liver cirrhosis

Nan Qin, Fengling Yang, Ang Li, Edi Prifti, Yanfei Chen, Li Shao, Jing Guo, Emmanuelle Le Chatelier, Jian Yao, Lingjiao Wu, Jiawei Zhou, Shujun Ni, Lin Liu, Nicolas Pons, Jean Michel Batto, Sean P. Kennedy, Pierre Leonard, Chunhui Yuan, Wenchao Ding, Yuanting Chen, Xinjun Hu, Beiwen Zheng, Guirong Qian, Wei Xu, S. Dusko Ehrlich et al.

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

来源: 科技日报 浏览次数:125

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