Abstract
In a recent publication, Ansari et al. identified gut microbiota as a critical mediator of the intestinal inflammatory response through epigenetic programming of host intestinal epithelium. Exposure to the microbiota induces Ten-Eleven-Translocation (TET)-dependent hypomethylation of genomic elements regulating genes associated with inflammatory response and colorectal cancer. Here, we discuss the impact of such a discovery on the understanding of how the intestinal microbiota may contribute to epigenetic reprogramming and influence the onset of colorectal tumorigenesis. Finally, we examine the prospect of TET inhibition strategies as a therapeutic and/or preventive approach for colorectal cancer in patients afflicted by inflammatory bowel disease.
Highlights
The authors found a high enrichment of binding sites for FoxA, Eklf and AP1 transcription factors in corresponding hypomethylated low-methylated regions. Those factors were previously linked to gut homeostasis and the inflammatory response [2]. These findings subscribe to the concept of a microbiota-dependent epigenetic landscape in the gut, based on previous genome-wide histone modification analyses showing that commensal bacteria regulate chromatin organization in intestinal immune cell subpopulations [4]
The authors reported that Ten-Eleven-Translocation 3 (TET3) enzyme expression was significantly up regulated in colonic crypt cells from GC mice vs. GF animals
The remodeling of the DNA methylation signature observed in response to pro-inflammatory insults in the presence of microbiota induces transcriptional changes characteristic of Colorectal cancer (CRC)
Summary
The majority of these hypomethylated low-methylated regions were associated with transcriptionally upregulated genes in GC colonic crypt cells compared to the GF group. These findings subscribe to the concept of a microbiota-dependent epigenetic landscape in the gut, based on previous genome-wide histone modification analyses showing that commensal bacteria regulate chromatin organization in intestinal immune cell subpopulations [4]. Previous studies have demonstrated that chronic inflammatory signals establish epigenetic silencing of a specific set of genes in colonic epithelial cells, which contribute to inflammation-induced transformation [4].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
