Dissecting the Interplay Mechanism between Epigenetics and Gut Microbiota: Health Maintenance and Disease Prevention

Abstract

The gut microbiota exists throughout the full life cycle of the human body, and it has been proven to have extensive impacts on health and disease. Accumulating evidence demonstrates that the interplay between gut microbiota and host epigenetics plays a multifaceted role in health maintenance and disease prevention. Intestinal microflora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification. Moreover, epigenetic factors can serve as mediators to coordinate gut microbiota within the host. Aiming to dissect this interplay mechanism, the present review summarizes the research profile of gut microbiota and epigenetics in detail, and further interprets the biofunctions of this interplay, especially the regulation of intestinal inflammation, the improvement of metabolic disturbances, and the inhibition of colitis events. This review provides new insights into the interplay of epigenetics and gut microbiota, and attempts to reveal the mysteries of health maintenance and disease prevention from this new perspective.

Keywords: SCFAs; epigenetics; gut microbiota; interplay mechanism; microRNA.

Figure 1

The Interplay between host epigenetic mechanisms and gut microbiota. Gut microbiota inhabit the intestinal tract and are in symbiosis harmoniously with the human body, constituting a microecology in a yin-yang dynamic balance. Once this balance is disrupted, various diseases may occur. The host regulates the diversity and composition of gut microbiota through miRNAs and other epigenetic factors. Intestinal flora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification in the host.

Figure 2

Host epigenetic factors regulate the gut microbiota in multiple progresses of diseases. The gut epithelium secretes a variety of miRNAs, which can enter microorganisms to affect their transcription and alter the microbial structure and diversity. The gut microbiota generates different metabolites (e.g., butyrate and bile acids) that can, in turn, regulate the host metabolism, including BMI, insulin secretion, and lipid production. Dietary intake of nutrients (e.g., folic acid, methionine, and vitamin B12) provides methyl donors that affect host DNA methylation, which may modulate the intestinal inflammatory state. Some microbial metabolites can modify DNA methylation, histone acetylation, and miRNAs, and impair the homeostasis of the intestinal environment, thereby reducing beneficial microbiota and increasing the richness of pathogenic bacteria, and inducing the development of colorectal cancer.

Figure 3

Gut microbiota and its metabolites affect health and diseases via multiple epigenetic pathways. Gut microbiota along with its metabolites (e.g., SCFAs) are involved in health and disease through multiple epigenetic mechanisms, including affecting transporter activities (e.g., DNMTs, HMT, HAT, and HDACs), providing methyl donors to participate in DNA methylation and histone modifications, and miRNAs that can lead to gene transcriptional modifications. These mechanisms can participate in a variety of biological processes, such as the maturation of IECs, the maintenance of intestinal homeostasis, inflammatory response, the development of metabolic disorders, and the prevention of colon cancer.