基于16S rDNA基因测序技术探索慢性肝病患者的肠道菌群特征

肝脏 ›› 2025, Vol. 30 ›› Issue (5): 683-689.

基于16S rDNA基因测序技术探索慢性肝病患者的肠道菌群特征

马驰, 杨涓, 郑盛, 付新年, 罗江焰, 王鑫鑫, 马笑盈, 毛孝周

671003 云南大理大理大学临床医学院(马驰);大理大学第二附属医院(杨涓,郑盛,付新年,罗江焰,王鑫鑫,马笑盈,毛孝周)

收稿日期:2024-02-12 出版日期:2025-05-31 发布日期:2025-07-04
通讯作者: 郑盛,Email:zheng_sheng523@163.com
基金资助:
云南省地方高校(部分)基础研究联合专项面上项目(2018FH001-076,2018FH001-080);云南省教育厅科学研究基金项目(2023J0926);大理大学第八期教育教学改革研究项目(2022JGYX08-01,2022JGYX08-02)

To explore the characteristics of intestinal flora in patients with chronic liver disease based on 16S rDNA gene sequencing technology

MA Chi¹, YANG Juan², ZHANG Sheng², FU Xin-nian², LUO Jiang-yan², WANG Xin-xin², MA Xiao-ying², MAO Xiao-zhou²

1. School of Clinical Medicine, Dali University,Yunnan 671003,China;
2. The Second Affiliated Hospital of Dali University,Yunnan Hospital,Kunming 650011,China

Received:2024-02-12 Online:2025-05-31 Published:2025-07-04
Contact: ZHANG Sheng,Email:zheng_sheng523@163.com

摘要/Abstract

摘要： 目的探索慢性肝病患者与健康人群的肠道菌群差异及关联。方法选择2023年2月至2023年8月就诊于云南省第三人民医院(大理大学第二附属医院)的60例慢性肝病患者(其中慢性乙型肝炎16例,肝硬化37例,肝细胞癌7例),以及37例健康志愿者。提取粪便样本DNA并采用16S rDNA高通量测序技术检测肠道菌群,进行菌群多样性及组成分析。结果在Alpha多样性方面,与健康对照组相比,各慢性肝病组患者肠道菌群的丰富度及多样性均有显著降低,且在慢性乙型肝炎→肝硬化→肝细胞癌进展过程中,菌群丰富度及多样性在不断下降。在物种丰度上,随着慢性乙型肝炎→肝硬化→肝细胞癌进展,大肠杆菌-志贺菌属(Escherlchia-Shigella)丰度不断升高。在属水平上筛选出的差异物种中,与健康对照组相比,各慢性肝病组的粪杆菌属(Faecalibacterium)、琼脂杆菌属(Agathobacter)、普氏菌属(Prevotella-9)、小杆菌属(Dialister)、罗氏菌属(Roseburia)、瘤胃球菌属(Ruminococcus)、粪球菌属(Coprococcus)、罕见小球菌属(Subdoligranulum)等8个菌属相对丰度降低。LEfSe分析显示不同慢性肝病阶段肠道优势菌属存在差异。结论慢性肝病组患者与健康对照组人群相比,具有显著性差异的肠道菌群特征,其中大肠杆菌-志贺菌属(Escherlchia-Shigella)丰度的改变可能介导慢性乙型肝炎→肝硬化→肝细胞癌的进展。并且随着慢性乙型肝炎→肝硬化→肝细胞癌疾病进展,肠道优势菌属亦在发生变化。

关键词: 慢性肝病, 肠道菌群, 16S rDNA测序, 多样性分析, 差异物种分析

Abstract: Objective By comparing the intestinal flora characteristics of different chronic liver disease patients and healthy volunteers, the differences and associations of intestinal flora between chronic liver disease patients and healthy volunteers were explored. Methods A total of 60 patients with chronic liver disease (including 16 patients with chronic hepatitis B, 37 patients with cirrhosis, and 7 patients with hepatocellular carcinoma) and 37 healthy volunteers were selected from the Third People's Hospital of Yunnan Province from February 2023 to August 2023.Fresh fecal samples were collected, DNA was extracted and 16S rDNA high-throughput sequencing technology was used to detect intestinal flora, and microbial diversity and composition were analyzed. Results In terms of alpha diversity, compared with the healthy control group, the intestinal flora richness and diversity of patients in each chronic liver disease group were significantly reduced, and the flora richness and diversity continued to decline during the progression of chronic hepatitis B→cirrhosis→hepatocellular carcinoma. In terms of species abundance, with the progression of chronic hepatitis B→cirrhosis→hepatocellular carcinoma, the abundance of Escherlchia-Shigella increased continuously.Among the distinct species screened at the generic level, compared to healthy controls, Faecalibacterium, Agathobacter, Prevotella-9, Dialister, Roseburia and Ruminococcus in each chronic liver disease groupThe relative abundance of eight bacteria genera, including Coprococcus and Subdoligranulum, decreased.LEfSe analysis showed that intestinal dominant bacterium was different in different stages of chronic liver disease. Conclusion Patients with chronic liver disease have significantly different intestinal flora characteristics compared with healthy controls, and changes in the abundance of Escherlchia-Shigella may mediate the progression of chronic hepatitis B→cirrhosis→hepatocellular carcinoma. And with the progression of chronic hepatitis B→cirrhosis→hepatocellular carcinoma disease, the intestinal dominant bacterium is also changing.

Key words: Chronic liver disease, Intestinal flora, 16S rDNA sequencing, Diversity analysis, Differential species analysis

马驰, 杨涓, 郑盛, 付新年, 罗江焰, 王鑫鑫, 马笑盈, 毛孝周. 基于16S rDNA基因测序技术探索慢性肝病患者的肠道菌群特征[J]. 肝脏, 2025, 30(5): 683-689.

MA Chi, YANG Juan, ZHANG Sheng, FU Xin-nian, LUO Jiang-yan, WANG Xin-xin, MA Xiao-ying, MAO Xiao-zhou. To explore the characteristics of intestinal flora in patients with chronic liver disease based on 16S rDNA gene sequencing technology[J]. Chinese Hepatolgy, 2025, 30(5): 683-689.

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