基于16S rDNA测序分析酒精性脂肪肝病进展中小鼠肠道菌群变化  

Analysis of gut microbiota changes in alcoholic fatty liver disease in progression based on 16S rDNA sequencing technology

作　　者：董晓伟 吴长亮 王振常[2] 覃素萍 何坚科 黄慧仪 DONG Xiaowei;WU Changliang;WANG Zhenchang;QIN Suping;HE Jianke;HUANG Huiyi(Guangxi University of Chinese Medicine,Nanning 530200,China;Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530201,China)

机构地区：[1]广西中医药大学,南宁530200 [2]广西中医药大学附属国际壮医医院,南宁530201

出　　处：《广西医科大学学报》2024年第8期1134-1140,共7页Journal of Guangxi Medical University

基　　金：广西特色壮瑶药医院制剂及产业化研究创新团队资助项目(No.GZKJ2309);广西中医药大学博士科研启动基金资助项目(No.XP020093)。

摘　　要：目的:采用16S rDNA测序技术分析酒精性脂肪肝病(AFLD)发展过程中小鼠肠道菌群的变化,并探讨小鼠AFLD进展的可能机制。方法:将60只雄性C57BL/6小鼠随机分为对照组(35只)和模型组(25只)。适应性喂养5 d后,对照组小鼠每天喂食Lieber-DeCarli对照流质饲料(TP4030C),模型组小鼠每天喂食含有4%乙醇的Lieber-DeCarli流质饲料(TP4030B),连续30 d后,采用苏木精—伊红(HE)染色法观察肝脏病理变化;16S rDNA测序法分析肠道菌群组成结构。结果:与对照组相比,AFLD模型组小鼠肠道菌群的α多样性结果显示其物种丰富度降低(P<0.05)。Beta多样性结果表明两组小鼠肠道菌群结构组成和丰度存在显著差异(P<0.05)。与对照组相比,模型组粪杆菌属(Faecalibaculum)、杜博菌属(Dubosiella)、异杆菌属(Allobaculum)、瘤胃球菌属UCG-013(Ruminococcaceae UCG-013)等菌属相对丰度升高,乳酸杆菌属(Lactobacillus)、毛螺菌属(Lachnospiraceae NK4A136 group)等菌属相对丰度降低。模型组小鼠肠道菌群在丙氨酸转移酶、谷胱甘肽水解酶和组蛋白乙酰转移酶通路活性显著增加(P<0.05)。结论:含4%乙醇的Lieber-DeCarli流质饲料成功构建了AFLD C57BL/6小鼠模型,AFLD小鼠肠道菌群的结构和组成均发生变化,酒精可能通过破坏肠道微生物稳态,增加丙氨酸转移酶、谷胱甘肽水解酶和组蛋白乙酰转移酶通路活性加快AFLD的进展。Objective:To analyze the changes of gut microbiota in the progression of alcoholic fatty liver disease(AFLD)using 16S rDNA sequencing technology,and to explore the possible mechanism of AFLD progression in mice.Methods:A total of 60 male C57BL/6 mice were randomly divided into control group(n=35)and model group(n=25).After adaptive feeding for 5 days,mice in the control group were fed a control Lieber-DeCarli fluid feeds(TP4030C)daily,and mice in the model group were fed Lieber-DeCarli fluid feeds(TP4030B)containing 4%ethanol daily.After 30 consecutive days,hematoxylin-eosin(HE)staining was used to observe the pathologi-cal changes of the liver.16S rDNA sequencing was used to analyze the composition and structure of gut microbio-ta.Results:Compared with the control group,Alpha diversity results of the gut microbiota of mice in the AFLD model group showed reduced species richness(P<0.05).Beta diversity results indicated significant differences in the structural composition and abundance of the gut microbiota of the two groups of mice(P<0.05).Com-pared with the control group,the relative abundance of Faecalibaculum,Dubosiella,Allobaculum,Ruminococca-ceaeUCG-013were higher in the model group,while the relative abundance of Lactobacillusand Lachnospirace-aeNK4A136group were lower in the model group.The activity of gut microbiota in alanyltransferase,glutathi-one hydrolase and histone acetyltransferase pathways was significantly increased in the model group of mice(P<0.05).Conclusion:AFLD C57BL/6 mouse model is successfully constructed on Lieber-DeCarli fluid feeds con-taining 4%ethanol,and both the structure and composition of the gut microbiota of AFLD mice are altered.Alco-hol may accelerate the progression of AFLD by disrupting gut microbial homeostasis and increasing the activities of alanyltransferase,glutathione hydrolase,and histone acetyltransferase pathways.

关 键 词：酒精性脂肪肝病 16S rDNA基因测序 肠道菌群 优势菌 

分 类 号：R575[医药卫生—消化系统]