Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic
Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic
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DOI：
10.1172/jci124196
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发表时间：
2019-04-01
影响因子：
15.9
通讯作者：
Sears, Cynthia L.
中科院分区：
文献类型：
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作者：
Tomkovich, Sarah;Dejea, Christine M.;Sears, Cynthia L.
在大约50%的结直肠癌(CRC)患者和大约13%的健康受试者的结肠粘膜上发现了粘液侵袭性细菌生物膜。在这里，我们测试了这样的假设，即人类结肠生物膜包括在CRC小鼠模型中具有致癌作用的微生物群落。从肿瘤患者(肿瘤和手术切除的正常组织)或来自接受结肠镜检查的健康人的生物膜阳性活检组织制备人生物膜阳性结肠粘膜的匀浆，以来自接受结肠镜检查的健康人的生物膜阴性的结肠活检组织的匀浆作为对照。12周后，在3种小鼠结肠肿瘤模型(无菌APC(Min)(Delta 850/+)；Il10(-/-)或APC(Min)(Delta 850/+)和无特定病原体APC(Min)(Delta 716/+)小鼠)中，生物膜阳性而不是生物膜阴性的人结肠粘膜匀浆诱导结肠癌形成。值得注意的是，来自健康结肠镜活检的生物膜阳性社区诱发结肠炎和肿瘤，类似于生物膜阳性肿瘤组织。到1周时，生物膜阳性的人肿瘤匀浆，而不是健康的活检组织，在小鼠结肠中显示出一致的细菌粘液入侵和生物膜形成。165rRNA基因测序和RNA-Seq分析确定了在生物膜阳性和生物膜阴性群落中定居的小鼠在组成和功能上的微生物区系差异。这些结果表明，人类结肠粘膜生物膜，无论是来自肿瘤宿主或接受结肠镜检查的健康人，在结直肠癌小鼠模型中都是致癌的。
Mucus-invasive bacterial biofilms are identified on the colon mucosa of approximately 50% of colorectal cancer (CRC) patients and approximately 13% of healthy subjects. Here, we test the hypothesis that human colon biofilms comprise microbial communities that are carcinogenic in CRC mouse models. Homogenates of human biofilm-positive colon mucosa were prepared from tumor patients (tumor and paired normal tissues from surgical resections) or biofilm-positive biopsies from healthy individuals undergoing screening colonoscopy; homogenates of biofilm-negative colon biopsies from healthy individuals undergoing screening colonoscopy served as controls. After 12 weeks, biofilm-positive, but not biofilm-negative, human colon mucosal homogenates induced colon tumor formation in 3 mouse colon tumor models (germ-free Apc(Min)(Delta 850/+);Il10(-/-)or Apc(Min)(Delta 850/+) and specific pathogen-free Apc(Min)(Delta 716/+) mice). Remarkably, biofilm-positive communities from healthy colonoscopy biopsies induced colon inflammation and tumors similarly to biofilm-positive tumor tissues. By 1 week, biofilm-positive human tumor homogenates, but not healthy biopsies, displayed consistent bacterial mucus invasion and biofilm formation in mouse colons. 165 rRNA gene sequencing and RNA-Seq analyses identified compositional and functional microbiota differences between mice colonized with biofilm-positive and biofilm-negative communities. These results suggest human colon mucosal biofilms, whether from tumor hosts or healthy individuals undergoing screening colonoscopy, are carcinogenic in murine models of CRC.