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 APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. 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）是结肠中最早的可在形态学上识别的病变，可通过使用对比染料喷雾的高清色谱内窥镜检出。尽管经常与同步性腺瘤相关，但它们在大肠肿瘤发展中，特别是在近端结肠中的作用仍不清楚。这项研究的目的是评估与近端ACF相关的结肠黏附细菌的概况，并研究它们与整个结肠中存在的同步息肉及其亚型的关系。这项回顾性研究包括了接受筛查或结肠镜检查的四十五名受试者。通过共聚焦组织切片内的原位杂交可以观察到粘附在ACF上皮和正常黏膜活检组织上的细菌细胞。与正常的粘膜相比，ACF在其细菌微生物组谱中显示出明显更高的异质性。我们表征的细菌群落结构之一与同步息肉的存在密切相关。最后，使用DNA质谱法评估ACF中存在的一组结肠直肠癌热点突变，我们发现三个APC基因突变与肠杆菌属的存在呈正相关，而KRAS突变与鲁米诺球菌呈正相关。该结果表明特定结肠相关细菌种类与体获得性CRC相关突变之间的潜在关系。总体而言，我们的研究结果表明，对正常粘膜黏附菌群的扰动可能是早期肿瘤形成的危险因素，这表明粘膜营养不良对组织微环境和ACF行为的潜在影响，可能促进它们向更高级的肿瘤形成发展。