KEY TAKEAWAYS
- The study aimed to investigate how gut and tissue microbes influence DNA methylation in CRC.
- Researchers noticed that gut microbiota significantly impact DNA methylation and contribute to CRC development.
Colorectal cancer (CRC) is an outcome of complex interactions between the host and their environment, including gut and tissue microbes. Recent research suggests that epigenetic regulation by gut microbiota plays a crucial role in modulating intestinal biology.
Zhi Liu and the team aimed to explore how gut and tissue microbes affect host DNA methylation in CRC.
They performed an inclusive analysis encompassing metagenomic sequencing of fecal samples from matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome profiling was conducted using 16S rRNA gene sequencing on the tumor (n = 24) and tumor-adjacent normal (n = 24) tissues in patients with CRC. Host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals.
The substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues were revealed. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Notably, a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues was observed, absent in tumor tissues. Furthermore, consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa were established.
The study concluded that gut microbiota and harmful bacteria play a key role in altering DNA methylation, affecting body balance, and contributing to CRC development. These findings highlight the complex host-environment interactions and suggest new treatment possibilities.
The research was funded by the National Key Research and Development Program, the National Natural Science Foundation of China (NSFC) grant, and the Key Society Development Project of Jiangsu Province to XL, along with the National Science Foundation of Jiangsu Higher Education Institutions to ZL, and the Major Scientific Project of Zhejiang Province to WF.
Source: https://pubmed.ncbi.nlm.nih.gov/38840170/
Liu Z, Zhang Q, Zhang H, et al.(2024). “Colorectal cancer microbiome programs DNA methylation of host cells by affecting methyl donor metabolism.” Genome Med. 2024 Jun 5;16(1):77. Doi: 10.1186/s13073-024-01344-1. PMID: 38840170.
