Abstract
Background: Epigenetic alterations, including DNA methylation, significantly contribute to colorectal cancer (CRC); the gut microbiota is also involved. However, studies on the possible role of microbiota in DNA methylation are limited. This study investigates the association between gut microbiota composition and high-methylated CRC (HMCC). Methods: Fecal and tumor tissue samples were collected from 86 patients with sporadic CRC. HMCC was defined based on the methylation status of 16 CpG sites of tumor-derived genomic DNA. 16S rRNA gene sequencing was performed to reveal the composition of the gut microbiota. The load of Fusobacterium nucleatum (F. nucleatum) in tumor tissues was assessed using quantitative polymerase chain reaction (qPCR). Results: HMCC was identified in 21 patients, whereas 65 were classified as having low-methylated CRC (LMCC). HMCC was significantly associated with proximal location, large diameter, undifferentiated histology, and high frequency of BRAF mutation. In gut microbial analyses, the relative abundances of 84 bacteria, including F. nucleatum, were significantly different between HMCC and LMCC. The load of F. nucleatum in CRC specimens was significantly correlated with its relative abundance in fecal samples and tended to be enriched in HMCC tissues. Conclusions: This study characterizes the gut microbiota profile in HMCC and suggests that bacteria, such as F. nucleatum, may contribute to HMCC pathogenesis through DNA methylation. Further studies are needed to determine whether the microbiome acts as a promoter or bystander in HMCC development.