患有家族性腺瘤多重症的患者含有致癌细菌的结肠生物膜
Christine M Dejea1,2, Payam Fathi1,2,3, John M Craig4
1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
概括
某些肠道细菌,如大肠杆菌和细菌,与遗传性结直肠癌 (CRC) 的癌前病变有关. 这些细菌会产生毒素,可能会加速瘤的发展.
科学领域:
- 微生物学
- 癌症学
- 胃肠病学
背景情况:
- 在偶发性结直肠癌 (CRC) 中,肠道微生物组的改变很常见.
- 遗传性CRC中与癌前病变相关的特定微生物群在很大程度上是未知的.
- 在家族性腺瘤多症 (FAP) 患者中,早年就会出现良性前体病变 (多).
研究的目的:
- 在患有家族性腺瘤多重症 (FAP) 的患者中研究结肠粘膜相关的微生物群.
- 在遗传性结直肠癌的早期阶段确定特定细菌及其毒素的存在和作用.
主要方法:
- 来自FAP患者和健康个体的结肠粘膜分析.
- 细菌生物膜的鉴定,特别是大肠杆菌和脆弱细菌.
- 编码毒素的基因量化: colibactin (*clbB*) 和 *Bacteroides fragilis* 毒素 (*bft*).
- 实验模型使用易患瘤的小鼠与大肠杆菌和肠毒性B.
主要成果:
- 在FAP患者的结肠粘膜中发现了不一致的细菌生物膜,主要是*Escherichia coli*和*Bacteroides fragilis*.
- 与健康个体相比,FAP患者中的 colibactin (*clbB*) 和 *Bacteroides fragilis* toxin (*bft*) 的基因显著增加.
- 与两种细菌共同殖民的小鼠表现出增加的互白素-17,DNA损伤,较快的瘤发作和比单个细菌菌株更高的死亡率.
结论:
- 结肠中的早期瘤病变与特定的致菌之间存在关联.
- 大肠杆菌和肠毒性B. fragilis的联合存在可能通过瘤毒素的产生和炎症促进结直肠瘤.
- 这些发现突显了肠道微生物组与遗传性结直肠癌的发病关系.
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