Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia

Abstract

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.

Human oral microbiome dysbiosis as a novel non-invasive biomarker in detection of colorectal cancer

“…These findings suggest that biomarkers based on the oral microbiota may help predict the risk of CRA and CRC. Hong et al found that microbiome dysbiosis in early aberrant crypt foci legion can be used as a biomarker for potential CRC development 55 . However, colonoscopy used in the study of Hong is an invasive method, whilst oral swab in our study is non-invasive that makes patients more compliant.…”

Microbiomes and Resistomes in Biopsy Tissue and Intestinal Lavage Fluid of Colorectal Cancer

“…Even though fecal microbiota partially reflects the microbiota at the mucus layer, differences between fecal and tissue microbiota are still evident. The bacterial clusters in IVF may provide greater insight into mucosal-specific colonic neoplasia due to their close interactions with epithelial and immune cells (Hong et al, 2019). As there is no unanimous conclusion in the advantages of different types of specimens, accurate comparisons between sample types in large sample sizes are needed, and a combinatorial approach may enable a sensitive and accurate evaluation of the gut microbiota.…”

Serrated neoplasia in the colorectum: gut microbiota and molecular pathways

“…66 A positive correlation between Ruminococcus gnavus and KRAS mutation in aberrant crypt foci samples was also described, although this finding was only reported in one study with a limited sample size. 69 As described previously, serrated neoplasia is characterized by high MLH1 deficiency, KRAS and BRAF mutation, 6,11,25,27 yet the association with F. nucleatum, B. fragilis, or R. gnavus remains unclear and needs to be explored in future studies.…”