Epigenetic Changes Induced by Bacteroides fragilis Toxin

Area of Science:

• Microbiology
• Genomics
• Cancer Biology

Background:

• Enterotoxigenic Bacteroides fragilis (ETBF) is prevalent in the gut microbiome and linked to colorectal cancer (CRC).
• ETBF-secreted Bacteroides fragilis toxin (BFT) promotes tumor formation in mice, but its epigenetic effects are largely unknown.
• Previous studies focused on BFT's impact on DNA methylation, leaving chromatin structure effects unexplored.

Purpose of the Study:

• To investigate the effects of BFT on gene expression and chromatin accessibility in colon epithelial cells (CECs).
• To identify epigenetic mechanisms by which BFT contributes to colorectal cancer development.

Main Methods:

• Treatment of HT29/C1 colon cancer cells with purified BFT.
• Transcriptome sequencing (RNA-seq) to analyze gene expression changes.
• Assay for transposase-accessible chromatin using sequencing (ATAC-seq) to assess chromatin accessibility.

Main Results:

• BFT treatment induced differential gene expression in CECs, particularly genes involved in host-microbe interactions.
• Increased chromatin accessibility sites were identified, correlating with enhancer regions and AP-1/ATF transcription factor binding.
• These accessible regions were enriched for differentially methylated regions (DMRs) commonly found in CRC.

Conclusions:

• BFT significantly alters the epigenetic landscape of colon epithelial cells, impacting gene expression and chromatin structure.
• These epigenetic changes provide novel insights into BFT's role in colorectal cancer pathogenesis.
• The findings establish a foundation for future in vivo studies on BFT's nuclear effects in CRC.