首页|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

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

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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(WN组),NAFLD患者菌液灌胃+SD大鼠组(WH组),健康人菌液灌肠+SD大鼠组(CN组),NAFLD患者菌液灌肠+SD大鼠组(CH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,WN、WH、CN、CH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WN、CN组相比,WH组、CH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WN组与WH组大鼠的肠道菌群组成差异有统计学意义(P<0.05);与WN、WH组相比,CN、CH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WN组相比,CN组大鼠的TC水平下降,且C H组大鼠的TC、TG水平较WH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脂质代谢紊乱;灌肠行人源性肠道微生物移植易诱发SD大鼠肝脏炎症反应,而灌胃干预可能更容易引起脂质代谢紊乱.健康人粪菌液可减轻NAFLD模型大鼠的炎症反应,改善脂质代谢紊乱,延缓NAFLD病情进展.
Evaluation of the safety and efficacy of different fecal bacteria transplantation based on intestinal flora of healthy people and nonalcoholic fatty liver disease patients
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 (WN group),NAFLD patient bacterial solution+gavage+SD rat group (WH group),healthy human bacterial solution+enema+SD rat group (CN group),NAFLD patient bacterial solution+enema+SD rat group(CH 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 WN,WH,CN and CH groups,AST,ALT,TC and TG levels were increased,and intestinal flora structure was significantly different among groups.Compared with WN and CN,pathological changes such as inflammatory response and ballooning were more obvious in WH 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 WN and WH groups,while there was no significant difference between CN and CH groups.Compared with WN and WH groups,lobular inflammation,balloon-like transformation and other overall pathological changes were more obvious in CN and CH groups,NAS scores were increased,ALT and AST levels were increased,and intestinal flora structure was significantly different between groups.However,TC level in CN group was decreased compared with WN group,and TC and TG levels in CH group were lower than those in WH group.Compared with group N,the liver tissues of rats in groups M and Z showed obvious pathological manifestations such as steatosis,lobular inflammation and balloon-like transformation,and the levels of NAS score,ALT,AST,TC and TG were significantly increased (P<0.05 ),and the levels of NAS score,ALT,AST,TC and TG were significantly higher than those in group Z than group M,with significant differences in microflora structure between groups.Conclusion:Transplantable human intestinal flora can induce liver pathological changes,abnormal liver enzymology and lipid metabolism disorders by affecting intestinal flora structure in SD rats.Compared with healthy people,fecal bacteria in NAFLD patients can aggravate liver inflammation and lipid metabolism disorder in SD rats;Pedestrian intestinal microbial transplantation by enema can easily induce liver inflammation in SD rats,while gavage intervention may be more likely to cause lipid metabolism disorders.Fecal bacteria solution of healthy human can alleviate the inflammatory response of NAFLD model rats,improve the disorder of lipid metabolism,and delay the progression of NAFLD disease.

fecal bacteria transplantationintestinal floranonalcoholic fatty liver diseasesecurity

郭丹、石媛媛、王雅、张涛

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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

粪菌移植 肠道菌群 非酒精性脂肪性肝病 安全性

2024

中西医结合肝病杂志
中国中西医结合学会,湖北中医学院

中西医结合肝病杂志

CSTPCD
影响因子:0.908
ISSN:1005-0264
年,卷(期):2024.34(12)