菌群移植对小鼠化疗相关性腹泻的改善作用  

Improvement effects of fecal microbiota transplantation on chemotherapy-induced diarrhea in mice

作　　者：杨秋雨 檀梦天 白净[2] 任行 张浚琪 杨勇 孙宇航[4] 李磊[3] 付泽娴 Yang Qiu-Yu;Tan Meng-Tian;Bai Jing;Ren Xing;Zhang Jun-Qi;Yang Yong;Sun Yu-Hang;Li Lei;Fu Ze-Xian(School of Clinical Medicine,Hebei University of Engineering,Handan,Hebei 056038,China;Department of Geriatric,Affiliated Hospital of Hebei Engineering University,Handan,Hebei 056038,China;Department of General Surgery,Affiliated Hospital of Hebei Engineering University,Handan,Hebei 056038,China;Medical Cosmetic and Plastic Surgery Center,Affiliated Hospital of Hebei Engineering University,Handan,Hebei 056038,China)

机构地区：[1]河北工程大学临床医学院,河北邯郸056038 [2]河北工程大学附属医院老年病科,河北邯郸056038 [3]河北工程大学附属医院普外中心,河北邯郸056038 [4]河北工程大学附属医院医学整形美容中心,河北邯郸056038

出　　处：《解放军医学杂志》2025年第3期261-268,共8页Medical Journal of Chinese People's Liberation Army

基　　金：邯郸市科技局基金(21422083309)。

摘　　要：目的探讨同种菌群移植(FMT)对小鼠化疗相关性腹泻(CID)的改善作用。方法15只C57BL/6N小鼠按照随机数分配、余数归组法分为空白对照组、CID模型组与CID+FMT组,每组5只。空白对照组不做任何干预,取其粪便制作粪菌悬液;CID模型组采用氟尿嘧啶(65 mg/kg)连续5 d腹腔注射构建CID小鼠模型,然后给予0.1 ml生理盐水隔日灌胃;CID+FMT组给予0.1 ml粪菌悬液隔日灌胃,干预7 d后采用氟尿嘧啶(65 mg/kg)连续5 d腹腔注射构建CID小鼠模型,至第14天结束实验。实验期间记录小鼠进食量和体重,实验结束时采用二氧化碳深度麻醉处死小鼠,采集肛门至盲肠肠管标本进行HE染色和组织学观察,采集粪便样本进行16S r RNA基因测序,采用Shannon指数、Simpson指数、Chao1算法对各组小鼠肠道菌群进行α多样性物种分析,采用相似性分析(Anosim)对各组小鼠肠道菌群的组间差异进行非参数检验,采用线性判别分析效应大小(LEf Se)和非度量多维尺度分析(NMDS)法分析各组小鼠肠道的优势菌群及相似性归类关系。结果CID模型组小鼠肛门至盲肠肠管长度较空白对照组明显缩短(P<0.05),CID+FMT组与CID模型组小鼠肛门至盲肠肠管长度比较差异无统计学意义(P>0.05)。CID模型组小鼠体重降低42.04%,空白对照组小鼠增重10.24%,两组间差异有统计学意义(P<0.05);CID+FMT组小鼠体重降低8.12%,与CID模型组小鼠比较体重下降明显缓解,差异有统计学意义(P<0.05)。HE染色结果显示,与空白对照组相比,CID模型组肠黏膜结构损伤较重,出现萎缩和变形,伴有炎性细胞浸润,病理学评分升高(P<0.05);与CID模型组相比,CID+FMT组肠黏膜完整性和隐窝细胞有所改善,损伤较轻,病理学评分差异无统计学意义(P>0.05)。菌群α多样性分析结果显示,三组Shannon、Simpson及Chao1指数差异有统计学意义(P<0.05);Anosim相似性分析和NMDS分析结果显示,与CID模型组相比,CID+FMT组肠道菌群�Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze theα-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained

关 键 词：菌群移植 化疗性腹泻 肠道菌群 高通量测序 

分 类 号：R6[医药卫生—外科学]