Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils.
Vancomycin-sensitive bacteria trigger development of colitis-associated colon cancer by attracting neutrophils.
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DOI：
10.1038/srep23920
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发表时间：
2016-04-06
影响因子：
4.6
通讯作者：
Isobe K
中科院分区：
文献类型：
--
作者：
Tanaka Y;Ito S;Isobe K
炎症性肠病会增加患结肠炎相关结肠癌（CAC）的风险。在活动性结肠炎或肿瘤发展阶段，共生细菌表现出动态易位。然而，肠道细菌组成的改变是否会导致 CAC 仍不清楚。为了阐明共生细菌对 CAC 发育的影响，我们采用了氧化偶氮甲烷 (AOM) 和葡聚糖硫酸钠 (DSS) 诱导的小鼠 CAC 模型，并用或不用抗生素治疗。此外，我们还分析了抗生素对骨髓细胞浸润、结肠炎症反应和结直肠癌形成的影响。我们发现万古霉素治疗显着抑制了肿瘤的发展。此外，AOM/DSS处理极大地诱导了Gr-1high/CD11bhigh中性粒细胞向结肠的浸润，从而导致肿瘤坏死因子α和诱导型一氧化氮合酶的产生。万古霉素治疗抑制了 AOM/DSS 诱导的中性粒细胞浸润。此外，万古霉素治疗大大减少了AOM/DSS诱导的NO自由基引起的结肠损伤和DNA损伤。我们的研究结果表明，万古霉素敏感细菌通过吸引中性粒细胞进入受损结肠组织来诱导结肠炎症和DNA损伤，从而促进肿瘤形成。
Inflammatory bowel disease confers an increased risk of developing colitis-associated colon cancer (CAC). During the active colitis or developing tumor stage, commensal bacteria show dynamic translocation. However, whether alteration of the bacterial composition in the gut causes CAC is still unclear. To clarify the effect of commensal bacteria on CAC development, we employed an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced murine CAC model treated with or without antibiotics. In addition, we analyzed the effects of antibiotics on infiltration of myeloid cells, colonic inflammatory responses, and colorectal cancer formation. We found that vancomycin treatment dramatically suppressed tumor development. In addition, AOM/DSS treatment greatly induced the infiltration of Gr-1high/CD11bhigh neutrophils to the colon, which led to the production of tumor necrosis factor α and inducible nitric oxide synthase. Vancomycin treatment suppressed the infiltration of neutrophils induced by AOM/DSS. Moreover, vancomycin treatment greatly reduced the colon injury and DNA damage caused by AOM/DSS-induced NO radicals. Our results indicate that vancomycin-sensitive bacteria induced colon inflammation and DNA damage by attracting neutrophils into damaged colon tissue, thus promoting tumor formation.