Science:在家族性息肉病人肠道里,有两种细菌促癌!
  • 对家族性腺瘤性息肉病(FAP)患者的结肠黏膜进行活组织检查,发现存在pks+大肠杆菌和肠毒性脆弱拟杆菌(ETBF)组成的细菌生物被膜,及两种菌产生的促肿瘤毒素的共表达;
  • 在小鼠模型中,相较于定殖单一菌株,pks+大肠杆菌和ETBF共同定殖可显著增加肿瘤数量和死亡率;
  • ETBF可降解粘液层,增加粘附于结肠粘膜的pks+大肠杆菌,后者释放colibactin导致结肠上皮细胞发生DNA损伤;
  • 两种菌共定殖可诱导结肠IL-17显著上升,加剧结肠肿瘤恶化。
主编推荐语
mildbreeze
这是昨天发表在Science上的一篇重量级文章,发现在患有家族性腺瘤性息肉病的结直肠癌遗传易感个体中存在结肠细菌被膜,主要由两种癌性细菌组成——产生不同癌性毒素(oncotoxin)的大肠杆菌和脆弱拟杆菌,并在相应小鼠模型中进行了验证,说明这两种细菌在结肠粘膜的持续共定殖,可在遗传易感个体中驱动肿瘤形成。这是继幽门螺杆菌和具核梭杆菌后,再次明确鉴定出的促进癌症的细菌,强烈推荐阅读。
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Science [IF:63.714]

Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria

家族性腺瘤性息肉病患者中的结肠生物被膜含有致瘤细菌

10.1126/science.aah3648

2018-02-02, Article

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Abstract:收起
Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of and Genes for colibactin () and toxin (), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with (expressing colibactin), and enterotoxigenic showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.

First Authors:
Christine Dejea

Correspondence Authors:
Cynthia L Sears

All Authors:
Christine Dejea,Payam Fathi,John M Craig,Annemarie Boleij,Rahwa Taddese,Abby L Geis,Xinqun Wu,Christina E DeStefano Shields,Elizabeth M Hechenbleikner,David L Huso,Robert A Anders,Francis M Giardiello,Elizabeth C Wick,Hao Wang,Shaoguang Wu,Drew M Pardoll,Franck Housseau,Cynthia L Sears

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