Hong Bo-Young, Ideta Takayasu, Lemos Bruno S, Igarashi Yuichi, Tan Yuliana, DiSiena Michael, Mo Allen, Birk John W, Forouhar Faripour, Devers Thomas J, Weinstock George M, Rosenberg Daniel W
1The Jackson Laboratory for Genomic Medicine, Farmington, CT USA.
2Department of Medicine, University of Connecticut Health, Farmington, CT USA.
NPJ Precis Oncol. 2019 Nov 14;3:29. doi: 10.1038/s41698-019-0101-6. eCollection 2019.
Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three gene mutations were positively associated with the presence of ., whereas mutations were positively correlated with . This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.
异常隐窝灶（ACF）是结肠中最早可通过高清染色内镜对比染料喷洒检测到的形态学可识别病变。尽管常与同步腺瘤相关，但其在结直肠肿瘤发生中的作用，尤其是在近端结肠中的作用仍不清楚。本研究的目的是评估与近端ACF相关的结肠黏附细菌谱，并研究它们与整个结肠中同步息肉的存在及亚型的关系。45名接受筛查或监测结肠镜检查的受试者纳入了这项回顾性研究。通过共聚焦组织切片原位杂交观察ACF上皮和正常黏膜活检组织上黏附的细菌细胞。与正常黏膜相比，ACF的细菌微生物组谱显示出显著更大的异质性。我们鉴定的一种细菌群落结构与同步息肉的存在密切相关。最后，使用DNA质谱法评估ACF中存在的一组结直肠癌热点突变，我们发现三个基因突变与……的存在呈正相关，而……个突变与……呈正相关。这一结果表明特定结肠相关细菌种类与体细胞获得的结直肠癌相关突变之间存在潜在关系。总体而言，我们的研究结果表明，正常黏附黏膜菌群的扰动可能构成早期肿瘤形成的危险因素，这表明黏膜生态失调对ACF的组织微环境和行为可能产生潜在影响，从而促进其向更晚期肿瘤形式进展。
