关键词: 粪菌移植, 肺炎克雷伯菌, 肝脓肿, 肠道菌群, 黏蛋白2

Abstract: This work aims to explore the possibility of fecal microbiota transplantation(FMT)to inhibit hypervirulent Klebsiella pneumoniae caused liver abscess(KLA)infection in mice and its related mechanism. The mice were randomly divided into three groups: Healthy, Kp and FMT. Kp group mice were orally inoculated with 10⁶ CFU of K.pneumoniae isolate; FMT group mice were given FMT(300 mg/mL, 0.3 mL)orally 24 h after K.pneumoniae isolate oral inoculation. Results showed that FMT effectively inhibited the KLA infection in mice at 48 h after K.pneumoniae isolate oral inoculation. The high-throughput sequencing analysis showed that FMT altered the intestinal microbiota composition which has been changed- DOI:10.3969/j.issn.1000-1565.2022.03.011粪菌移植对肺炎克雷伯菌所致小鼠肝脓肿感染的抑制作用王子逸儒¹,朱冬青¹,付金文¹,程宝乾²,凌宗欣³,陈楠¹(1. 河北大学 基础医学院,河北 保定 071000;2. 河北医科大学 临床学院, 河北 石家庄 050031;3.浙江大学 医学院,附属第一医院,传染病诊治国家重点实验室, 浙江 杭州 310003)摘 要:探讨粪菌移植(FMT)对高致病性肺炎克雷伯菌(Klebsiella pneumoniae)所致小鼠肝脓肿(KLA)感染的抑制作用及相关机制. 小鼠随机分为对照(Healthy)组、肺炎克雷伯菌(Kp)组和干预(FMT)组. Kp组小鼠经口灌胃10⁶ CFU K1血清型肺炎克雷伯菌;FMT组在给菌24 h后经口灌胃给予正常小鼠粪菌悬液(300 mg/mL,0.3 mL). 结果表明,与Kp组相比,FMT处理明显降低了小鼠KLA感染率;16S rRNA高通量测序分析表明,FMT显著改变了小鼠肠道菌群组成,包括增加了Alloprevotella、norank_f_Muribaculaceae等益生菌的丰度;同时FMT处理明显降低了小鼠血清TNF-α和胃肠内防御素分子浓度,同时增加了肠黏蛋白2(MUC2)的表达. 因此,肠道菌群和免疫防御因子可能一起参与了FMT对高致病性肺炎克雷伯菌所致小鼠KLA感染的抑制作用. 关键词:粪菌移植;肺炎克雷伯菌;肝脓肿;肠道菌群;黏蛋白2中图分类号:R378 文献标志码:A 文章编号:1000-1565(2022)03-0295-08Fecal microbiota transplantation inhibited Klebsiella pneumoniae caused liver abscess infection in miceWANG Ziyiru¹, ZHU Dongqing¹, FU Jinwen¹,CHENG Baoqian², LING Zongxin³, CHEN Nan¹(1.School of Basic Medical Sciences, Hebei University, Baoding 071000, China; 2.College of Clinical Medicine, Hebei Medical University, Shijiazhuang 050031, China; 3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China)Abstract: This work aims to explore the possibility of fecal microbiota transplantation(FMT)to inhibit hypervirulent Klebsiella pneumoniae caused liver abscess(KLA)infection in mice and its related mechanism. The mice were randomly divided into three groups: Healthy, Kp and FMT. Kp group mice were orally inoculated with 10⁶ CFU of K.pneumoniae isolate; FMT group mice were given FMT(300 mg/mL, 0.3 mL)orally 24 h after K.pneumoniae isolate oral inoculation. Results showed that FMT effectively inhibited the KLA infection in mice at 48 h after K.pneumoniae isolate oral inoculation. The high-throughput sequencing analysis showed that FMT altered the intestinal microbiota composition which has been changed- 收稿日期:2021-10-22 基金项目:河北省高等学校科学技术研究项目青年项目(QN2020111);河北省博士后科研项目(B2017003032);河北大学优秀青年科研创新团队(科技类)项目(2020-8);河北大学医学学科培育项目(2020B10);河北大学大学生创新创业项目(2021292) 第一作者:王子逸儒(1997—),女,河北易县人,河北大学在读硕士研究生,主要从事肠道微生态与疾病的相关研究.E-mail:799241689@qq.com 通信作者:陈楠(1981—),女,河北安国人,河北大学副教授,主要从事肠道微生态与疾病的相关研究.E-mail:cnadyheu@126.com第3期王子逸儒等:粪菌移植对肺炎克雷伯菌所致小鼠肝脓肿感染的抑制作用by K.pneumoniae oral inoculation, including the up-regulation of the abundance of the probiotics Alloprevotella, norank_f_Muribaculaceae and so on. FMT also reduced the levels of defensins in intestine and stomach, inflammatory cytokine TNF-α in serum, and increased the concentration of mucin 2 in intestine. Therefore, the intestinal microbiota and immune defense factors may be involved in the inhibition of FMT against liver abscess infection caused by hypervirulent K.pneumoniae in mice.

Key words: fecal microbiota transplantation, Klebsiella pneumoniae, liver abscess, intestinal microbiota, mucin 2