健康人和NAFLD患者肠道菌群对不同粪菌移植途径大鼠的安全性及效果评价  

Evaluation of the safety and efficacy of different fecal bacteria transplantation based on intestinal flora of healthy people and nonalcoholic fatty liver disease patients

作　　者：郭丹 石媛媛 王雅[1] 张涛[1] GUD Dan;SHI Yuan-yuan;WANG Ya;ZHANGT Tao(First Affiliated Hospital of Hunan University of Chinese Medicine(Changsha Hunan,410007),China.)

机构地区：[1]湖南中医药大学第一附属医院肝病/感染性疾病科,湖南长沙410007

出　　处：《中西医结合肝病杂志》2024年第12期1088-1095,共8页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家自然基金联合基金项目(No.U21A20413);湖南省自然基金面上项目(No.2022JJ30459);长沙市自然科学基金重点课题(No.kq2208201);湖南省卫生健康委科研计划项目(No.B202303105937);湖南中医药大学研究生创新课题(No.2022CX145)。

摘　　要：目的:基于非酒精性脂肪性肝病(NAFLD)患者和健康人的肠道菌群通过灌胃或灌肠不同粪菌移植(FMT)途经对SD大鼠和NFLAD模型大鼠的影响,探究紊乱的肠道菌群对NAFLD发生发展的潜在因果关系,评估健康人粪菌液对NAFLD模型大鼠的影响。方法:健康雄性SD大鼠35只,随机分为7组:空白组(N组)、健康人菌液灌胃+SD大鼠组(W N组),NAFLD患者菌液灌胃+SD大鼠组(W H组),健康人菌液灌肠+SD大鼠组(C N组),NAFLD患者菌液灌肠+SD大鼠组(C H组),NAFLD大鼠模型组(M组),健康人菌液灌胃组+NAFLD大鼠模型(Z组),每组5只。实验结束后,比较各组SD大鼠的一般情况、肝组织病理、肝酶学指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)]、血脂水平(TC、TG)及肠道菌群特征。结果:与N组相比,W N、W H、C N、C H组大鼠肝组织局部可见少量炎性细胞浸润及气球样变,AST、ALT、TC、TG水平升高,且组间肠道菌群结构差异显著(P<0.05);与W N、C N组相比,W H组、C H组大鼠的炎性反应、气球样变等病理变化更明显,NAFLD活动积分(NAS)增加,ALT、AST、TC、TG水平升高,其中W N组与W H组大鼠的肠道菌群组成差异有统计学意义(P<0.05);与W N、W H组相比,C N、C H组大鼠的小叶炎症、气球样变等病理改变更明显,NAS评分增加,ALT、AST水平上升,组间肠道菌群结构差异有统计学意义,但与W N组相比,C N组大鼠的TC水平下降,且C H组大鼠的TC、TG水平较W H组偏低;与N组相比,M组、Z组大鼠肝组织可见明显的脂肪变性、小叶炎症和气球样变等病理表现,NAS、ALT、AST、TC、TG水平显著上升(P<0.05),与M组比较,Z组大鼠NAS、ALT、AST、TC、TG水平降低,组间菌群结构差异有统计学意义(P<0.05)。结论:移植人源性肠道菌群可通过影响SD大鼠肠道菌群结构改变,诱导肝脏病理变化、肝酶学异常及脂质代谢紊乱;与健康人菌液相比,NAFLD患者粪菌会加重SD大鼠的肝脏炎症反应和Objective:This study explores the potential causal relationship between dysregulated gut microbiota and the progression of non-alcoholic fatty liver disease(NAFLD).Using fecal microbiota transplantation(FMT)via oral gavage or enema,gut microbiota from NAFLD patients and healthy individuals were introduced into Sprague-Dawley rats and NAFLD model rats.Furthermore,the study evaluates the therapeutic effects of FMT from healthy donors on NAFLD model rats.Methods:Thirty-five male SD rats were randomly divided into blank group(group N),healthy human bacterial solution+gavage+SD rat group(W N group),NAFLD patient bacterial solution+gavage+SD rat group(W H group),healthy human bacterial solution+enema+SD rat group(C N group),NAFLD patient bacterial solution+enema+SD rat group(C H group).NAFLD rat model group(group M),NAFLD rat model+healthy human bacterial solution group(group Z),5 mice in each group.After the experiment,The liver histomatology,liver enzymology index(ALT,AST),lidexes levels(TC,TG,GLU)and intestinal flora characteristics of all groups were compared.Results:Compared with group N,a small amount of inflammatory cell infiltration and balloon-like transformation were observed locally in the liver tissue of rats in W N,W H,C N and C H groups,AST,ALT,TC and TG levels were increased,and intestinal flora structure was significantly different among groups.Compared with W N and C N,pathological changes such as inflammatory response and ballooning were more obvious in W H and CH groups,NAS scores were increased,and ALT,AST,TC and TG levels were increased.There was a significant difference in intestinal flora composition between W N and WH groups,while there was no significant difference between C N and C H groups.Compared with WN and W H groups,lobular inflammation,balloon-like transformation and other overall pathological changes were more obvious in C N and C H groups,NAS scores were increased,ALT and AST levels were increased,and intestinal flora structure was significantly different between groups.However,TC lev

关 键 词：粪菌移植 肠道菌群 非酒精性脂肪性肝病 安全性 

分 类 号：R575.5[医药卫生—消化系统]