Dejea Christine M, Fathi Payam, Craig John M, Boleij Annemarie, Taddese Rahwa, Geis Abby L, Wu Xinqun, DeStefano Shields Christina E, Hechenbleikner Elizabeth M, Huso David L, Anders Robert A, Giardiello Francis M, Wick Elizabeth C, Wang Hao, Wu Shaoguang, Pardoll Drew M, Housseau Franck, Sears Cynthia L
Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Science. 2018 Feb 2;359(6375):592-597. doi: 10.1126/science.aah3648. Epub 2018 Feb 1.
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.
散发性结直肠癌(CRC)患者的肠道微生物群组成常常存在异常;然而,遗传性CRC癌前病变相关的微生物群在很大程度上仍不为人知。我们研究了家族性腺瘤性息肉病(FAP)患者的结肠黏膜,这些患者在生命早期会出现良性前驱病变(息肉)。我们发现了斑驳状细菌生物膜,其主要由[具体细菌名称1]和[具体细菌名称2]组成。与健康个体相比,编码分泌型致癌毒素的大肠杆菌素(clb)和[毒素名称2]毒素([毒素名称2])的基因在FAP患者的结肠黏膜中高度富集。与单独感染任一菌株的小鼠相比,共同定殖有表达大肠杆菌素的[具体细菌名称1]和产肠毒素的[具体细菌名称2]的易患肿瘤小鼠,其结肠中的白细胞介素-17增加,结肠上皮细胞出现DNA损伤,肿瘤发生更快,死亡率更高。这些数据表明结肠早期肿瘤形成与致癌细菌之间存在意想不到的联系。