Dejea Christine M, Wick Elizabeth C, Hechenbleikner Elizabeth M, White James R, Mark Welch Jessica L, Rossetti Blair J, Peterson Scott N, Snesrud Erik C, Borisy Gary G, Lazarev Mark, Stein Ellen, Vadivelu Jamuna, Roslani April C, Malik Ausuma A, Wanyiri Jane W, Goh Khean L, Thevambiga Iyadorai, Fu Kai, Wan Fengyi, Llosa Nicolas, Housseau Franck, Romans Katharine, Wu XinQun, McAllister Florencia M, Wu Shaoguang, Vogelstein Bert, Kinzler Kenneth W, Pardoll Drew M, Sears Cynthia L
Departments of Microbiology and Immunology and.
Departments of Surgery.
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18321-6. doi: 10.1073/pnas.1406199111. Epub 2014 Dec 8.
Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
环境因素显然会影响结直肠癌（CRC）的发病率，但这些因素发挥作用的机制尚不清楚。一个主要的候选因素是结肠微生物群的改变。在这里，我们表明黏膜微生物群的组织是与一部分CRC相关的关键因素。我们发现侵袭性多微生物细菌生物膜（细菌聚集体），这种结构以前与非恶性肠道病变有关，在右侧肿瘤（15例CRC中的13例，4例腺瘤中的4例）中几乎普遍存在（89%），而在左侧肿瘤中仅占12%（15例CRC中的2例，2例腺瘤中的0例）。令人惊讶的是，患有生物膜阳性肿瘤的患者，无论是癌症还是腺瘤，在远离肿瘤的无肿瘤黏膜上都有生物膜。细菌生物膜与结肠上皮细胞E-钙黏蛋白减少、上皮细胞IL-6和Stat3激活增强以及正常结肠黏膜中隐窝上皮细胞增殖增加有关。高通量测序显示，无论生物膜状态如何，均未发现与肿瘤相关的一致细菌属。然而，主坐标分析显示，远离肿瘤本身的配对正常黏膜上的生物膜群落与肿瘤微生物群聚集在一起，而不是与来自肿瘤宿主的生物膜阴性正常黏膜细菌群落聚集在一起。结肠黏膜生物膜检测可能预示散发性CRC发生风险增加。
