AI Article Synopsis

  • The study examines the link between changes in gut bacteria and DNA methylation of tumor suppressor genes (TSGs) in colorectal cancer (CRC) using genetic sequencing on tissue biopsies from various stages of the disease.
  • Researchers found that the bacteria Fusobacterium nucleatum and Hungatella hathewayi contribute to increased DNA methylation, which can regulate the expression of important TSGs like CDX2 and MLH1.
  • The findings suggest that these bacteria promote CRC by activating DNA methyltransferases, leading to enhanced cell proliferation in the colonic tissue.

Article Abstract

Background: Altered microbiome composition and aberrant promoter hypermethylation of tumor suppressor genes (TSGs) are two important hallmarks of colorectal cancer (CRC). Here we performed concurrent 16S rRNA gene sequencing and methyl-CpG binding domain-based capture sequencing in 33 tissue biopsies (5 normal colonic mucosa tissues, 4 pairs of adenoma and adenoma-adjacent tissues, and 10 pairs of CRC and CRC-adjacent tissues) to identify significant associations between TSG promoter hypermethylation and CRC-associated bacteria, followed by functional validation of the methylation-associated bacteria.

Results: Fusobacterium nucleatum and Hungatella hathewayi were identified as the top two methylation-regulating bacteria. Targeted analysis on bona fide TSGs revealed that H. hathewayi and Streptococcus spp. significantly correlated with CDX2 and MLH1 promoter hypermethylation, respectively. Mechanistic validation with cell-line and animal models revealed that F. nucleatum and H. hathewayi upregulated DNA methyltransferase. H. hathewayi inoculation also promoted colonic epithelial cell proliferation in germ-free and conventional mice.

Conclusion: Our integrative analysis revealed previously unknown epigenetic regulation of TSGs in host cells through inducing DNA methyltransferase by F. nucleatum and H. hathewayi, and established the latter as CRC-promoting bacteria. Video abstract.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367367PMC
http://dx.doi.org/10.1186/s40168-020-00847-4DOI Listing

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