肝硬化患者TIPS术后肠道菌群特征性改变及其与临床指标的相关性研究  

Changes in characteristics of gut microbiota and their correlation with clinical indicators in cirrhosis patients after transjugular intrahepatic portosystemic shunt

作　　者：李胜鹏 肖续 周安 谢卓 赵泳冰 徐征国 杨仕明 唐波 LI Shengpeng;XIAO Xu;ZHOU An;XIE Zhuo;ZHAO Yongbing;XU Zhengguo;YANG Shiming;TANG Bo(Department of Gastroenterology,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037,China)

机构地区：[1]陆军军医大学第二附属医院消化内科,重庆400037

出　　处：《陆军军医大学学报》2024年第12期1425-1433,共9页Journal of Army Medical University

摘　　要：目的比较既往行颈静脉肝内门体分流术(transjugular intrahepat portosystemic stent-shunt,TIPS)手术的肝硬化患者与未经TIPS手术的肝硬化患者的肠道菌群,探索在肝硬化患者中,TIPS手术与肠道菌群的关系,为基于肠道菌群干预改善肝硬化TIPS手术预后提供新思路。方法行TIPS手术的肝硬化患者为手术组,未经TIPS手术的肝硬化患者为对照组,收集患者大便标本行16S rRNA测序分析,并分析肠道菌群与临床指标相关性。结果两组患者在性别、年龄、体重指数(BMI)、病因等基线资料上均无显著差异(P>0.05),但临床血清学指标(如HGB,RBC,ALP,ALB,TBIL,PT,INR,APTT,UREA等)有显著差异(P<0.05)。手术组与对照组相比,α多样性无统计学差异(P>0.05),β多样性差异明显(P<0.01),手术组Bacteroides(拟杆菌属)明显增多(P<0.01),而对照组Bifidobacterium(双歧杆菌属)明显增多(P<0.05)。肠道菌群功能预测分析显示,手术组较对照组D-谷氨酰胺和D-谷氨酸代谢显著上升(P<0.05),次级胆汁酸生物合成(P<0.05)也显著上升。临床指标与菌群相关性分析中发现,总胆红素(TBIL)及直接胆红素(DBIL)与Bacteroides(拟杆菌属)、次级胆汁酸代谢通路显著相关。结论肝硬化TIPS术后患者肝硬化对照者相比,肠道菌群存在特征性改变,Bacteroides(拟杆菌属)可能参与胆汁酸代谢调控进而影响TIPS术后血胆红素水平升高。Objective To compare the differences in gut microbiota between cirrhosis patients receiving transjugular intrahepatic portosystemic shunt(TIPS)and those not,and explore the relationship between TIPS surgery and gut microbiota in order to provide new ideas for improving the prognosis of cirrhosis patients after TIPS surgery based on gut microbiota.Methods Those who had received TIPS surgery previously were assigned into the operation group,and those without the surgery served as the control group.Their stool samples were collected for 16S rRNA sequencing,and the correlation between gut microbiota and clinical indicators was analyzed.Results There were no significant differences in gender,age,body mass index(BMI),etiology and other baseline data between the 2 groups(P>0.05),but obvious differences were observed in clinical serological indicators between them,including INR,APTT,RBC and PT counts,and HGB,ALP,ALB,total bilirubin(TBIL),and URE levels(P<0.05).No statistical difference in alpha diversity was observed between the operation group and the control group(P>0.05),but beta diversity was obviously different(P<0.01),among which Bacteroides was increased in the operation group(P<0.01)and Bifidobacterium was increased in the control group(P<0.05).The function prediction analysis of gut microbiota showed that the metabolism of D-glutamine and D-glutamate(P<0.05)and biosynthesis with secondary bile acids(P<0.05)were up-regulated in the operation group compared with the control group.Correlation analysis between clinical indicators and flora indicated that TBIL and direct bilirubin(DBIL)were significantly correlated with the metabolic pathways of Bacteroides and Secondary bile acids biosynthesis.Conclusion Characteristic changes in gut microbiota are found in cirrhosis patients with and without TIPS surgery.Bacteroides may be involved in the regulation of metabolism of bile acids and thus increase bilirubin level.

关 键 词：TIPS手术 肠道菌群 16S rRNA 拟杆菌属 双歧杆菌属 

分 类 号：R372[医药卫生—病原生物学] R446.112[医药卫生—基础医学] R657.31