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湿热证大肠癌患者肠道菌群对AOM/DSS小鼠肠癌发生的影响

Influence of gut microbiota in colorectal cancer patients with damp-heat syndrome on the tumorigenesis of colorectal cancer in AOM/DSS mice

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【作者】 周晔禄; 赵玲; 贾茹; 饶希午; 侯新新; 岑戎; 张怡; 冯媛媛; 刘宁宁; 周利红; 王炎; 李琦;

【Author】 ZHOU Ye-lu;ZHAO Ling;JIA Ru;RAO Xi-wu;HOU Xin-xin;CEN Rong;ZHANG Yi;FENG Yuan-yuan;LIU Ning-ning;ZHOU Li-hong;WANG Yan;LI Qi;Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine;Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine;

【通讯作者】 李琦;

【机构】 上海中医药大学附属曙光医院; 上海中医药大学中西医结合研究院;

【摘要】 目的:探讨湿热证大肠癌患者肠道菌群结构特点及其对肠癌发生的影响。方法:通过16S rRNA测序分析湿热证和无明显证候大肠癌患者肠道菌群特征,并将其粪菌提取液对伪无菌小鼠进行粪菌移植,同时通过AOM/DSS诱导小鼠肠癌发生。观察小鼠的体质量、成瘤数,比较各组细胞因子表达水平。结果:与无明显证型大肠癌患者比较,湿热证大肠癌患者具有显著不同的微生物群落结构,其中致病菌(如大肠杆菌属、别样杆菌属、肠球菌属、Intestinibacter菌属、嗜胆菌属等)的丰度明显增高,此外以大肠杆菌为代表的产LPS病原菌明显富集(P<0.01)。对AOM/DSS小鼠模型进行粪菌移植后,相较于无明显证型粪菌移植小鼠,湿热证粪菌移植小鼠体质量明显减轻(P<0.01),结肠肿瘤形成增多(P<0.01),且促炎细胞因子IL-6 mRNA表达显著增高(P<0.05)。结论:湿热证大肠癌患者具有致病菌增多和以LPS合成细菌增多为主要特点的肠道菌群结构,其肠道菌通过粪菌移植后可促进AOM/DSS小鼠肠癌发生。

【Abstract】 Objective: To explore profile of gut flora structure in colorectal cancer(CRC) patients with damp-heat syndrome(DHS) and the effects on the occurrence of CRC. Methods: The characteristics of fecal bacteria in CRC patients with different syndromes were sequenced by 16S rRNA analysis. Fecal bacterial suspensions prepared from patients were transplanted into pseudo germ-free mice, and AOM/DSS was used to induce the tumorigenesis in mice. Body weight, tumor number and expression levels of colonic pro-inflammatory cytokines were observed. Results: A significant difference in fecal microbial communities was found between CRC patients with DHS and uncertain syndrome(US). In the DHS group, the abundance of pathogenic bacteria(Escherichia-Shigella, Alistipes, Enterococcus, Intestinibacter, Bilophila, etc.) were significantly increased,of which lipopolysaccaride(LPS) producing bacteria represented by Escherichia-Shigella were more abundant in DHS cases than that of US cases(P<0.01). Following fecal microbiota transplantation(FMT) in AOM/DSS mouse model, more body weight losses(P<0.01), more colonic tumors(P<0.01) and higher mRNA expression of pro-inflammation cytokines IL-6(P<0.05)were observed in FMT-DHS group than those of FMT-US group. Conclusion: CRC patients with DHS have the special structure of intestinal microbiota characterized by the increase of pathogenic bacteria and LPS-producing bacteria, and the characteristic microbiota of DHS can upregulate the level of colonic inflammation and promote the tumorigenesis in AOM/DSS mice.

【基金】 国家自然科学基金重点项目(No.81830120);上海市炎症性肿瘤转化病证生物学前沿研究基地(No.2021KJ03-12);上海市科学技术委员会科研计划项目(No.19401972200);上海市浦东新区卫健委联合攻关项目(No.PW2020D-4)~~
  • 【文献出处】 中华中医药杂志 ,China Journal of Traditional Chinese Medicine and Pharmacy , 编辑部邮箱 ,2022年05期
  • 【分类号】R273
  • 【下载频次】327
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