Fig. 1

Effect of the gut microbiome on the colon epithelial cell genome and epigenome. a Enterotoxigenic Bacteroides fragilis (ETBF) and pks + Escherichia coli cause DNA damage in CECs that is mediated by B. fragilis toxin (BFT) and colibactin, respectively. Enterococcus faecalis, through impact on macrophages, induces chromosomal instability and tumor-inducing DNA mutations in cancer driver genes. b Antibiotics, germ-free mice, and specific microbes (Bifidobacterium infantis, Lactobacillus acidophilus, Klebsiella species, and ETBF) have been used to show that gut microbes induce both the hypermethylation and the hypomethylation of genes belonging to pathways that are dysregulated in colorectal cancer (CRC). c Antibiotics and germ-free mice have been used to show that gut microbes do not generally affect global chromatin structure in CECs, but do cause changes in the accessibility of transcription factor binding sites, in histone modifications, and in the location of those modified histones. These modifications often affect the promoter and enhancer regions of genes that belong to pathways that are dysregulated in CRC. d Antibiotics, germ-free mice, and specific microbes (Bacteroides acidifaciens, Lactobacillus johnsonii, and Fusobacterium nucleatum) have been used to show that gut microbes alter the expression of oncomiRNAs and anti-oncomiRNAs in CECs. They also alter the expression of long non-coding RNAs (lncRNAs) that are involved in G protein-coupled receptor (GPCR) and transforming growth factor (TGF) signaling. Abbreviations: ETS e26 transformation-specific, IRF interferon regulatory factor, miRNA microRNA, ROS reactive oxygen species, STAT signal transducer and activator of transcription