Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Abstract

In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

Interspecies Communication in Holobionts by Non-Coding RNA Exchange

“…Selected human and animal studies clearly showed the existence of communication axes between the intestine and other organs that are extended beyond the gut, and that contribute to the function and dysfunction of distant organ systems [125,126]. Gut microbiome dysbiosis has been correlated with several types of tumors, suggesting the direct connection between the microbiota and tumor proliferation [127,128].…”

Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer

“…It has been considered as an "invisible organ" of human body [10], and contains at least 150 times more genes in total than the host genome [11]. As an "invisible organ", intestinal microbiota or their metabolites can, in fact, significantly impact human health, causing diseases such as obesity [12], diabetes [13], fatty liver disease [14], hypertension and cardiovascular disease [15], CRC [16], etc.…”

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

“…The results of this study will not be available for many years to come. A key reason for caution regarding potential long-term consequences of FMT is the ever-increasing list of diseases associated with the microbiome [54]. Thus, manipulation of the gut microbiome, particularly with wholesale replacement via FMT, could have varied and unforeseeable consequences that are only identifiable after the fact [51].…”