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Epigenetics, the study of genetic expression influenced by environmental factors, relies heavily on the composition and functioning of the gut microbiome. This emerging field encompasses all factors above genetics that play a role in altering gene expression, without changing the underlying DNA sequence.
Also referred to as the ‘second genome,’ the gastrointestinal tract inhabits over one thousand diverse microbial species, encoding an estimated five million genes. The GI microbiome, therefore, represents a vast opportunity to favorably shape genetic expression.
Gut microbiota have modulatory effects on genetic expression and influence various factors related to health, as demonstrated in a 2024 study. Nutrition, sleep and circadian rhythm, exercise, stress, relationships, and environmental insults all influence the activation or silencing of particular genes. The gut microbiome is also affected by these factors, having profound influence on genetic expression.
A growing body of research demonstrates a strong interrelationship between epigenetics and the GI microbiome, as evidenced in a 2024 review published in the International Journal of Molecular Sciences. This review revealed direct interactions between the GI microbiome and epigenetic mechanisms, including DNA methylation, histone modifications and noncoding RNA.
These processes influence genetic expression through the synthesis of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan metabolites (Trps), that support in modulating inflammation, immune health and intestinal permeability.
SCFAs, such as butyrate, have been shown to exert epigenetic regulatory mechanisms by influencing DNA methylation and histone acetylation, thereby altering chromatin structure and gene expression.
Bile acid metabolites influence gene expression by binding to G-protein-coupled receptors (GPCRs), triggering signaling pathways that impact immune function and metabolism. Tryptophan metabolites maintain intestinal homeostasis and modulate immune function and restoration.
By influencing DNA methylation and histone modifications, the gut microbiota significantly affect cellular epigenetic mechanisms. Microbial metabolites serve as integral messengers in the interplay between microbiota and epigenetics, supporting regulatory mechanisms beneficial to health.
GI metabolites support modulation of immune cell activity, influence the development and function of immune-suppressive regulatory T-cells, and inhibit inflammatory responses. Metabolites produced by the gut are foundational to the gut-epigenetics connection, as supported by a 2024 study published in Microbiological Research.
Recent studies reveal dynamic interactions between epigenetic modifications and gut microbiota composition, indicating that epigenetic regulation has a bidirectional effect on modulating composition, as evidenced in a 2024 review published in Cell Press. This bidirectional "epigenome–microbiome axis” underscores this profound relationship and allows the host to shape its microbiome through alterations that influence gene expression and noncoding RNA activity.
A bidirectional relationship exists between our genes and microbial variations. Nutrition and lifestyle factors modulate alterations in gut microbiota and microbiota-derived metabolites, important for energy, digestion, immune function, hormonal balance, and nervous system health.
The diversity and composition of the gut microbiome are regulated through microRNA and other epigenetic mechanisms. Microbial metabolites have been shown to influence DNA methylation and histone modifications, underscoring their effects on epigenetic pathways.
Epigenetic dysregulation has emerged as a novel biomarker of aging, while contributing to altered immune responses, such as immunosenescence, an insufficient response in immune function and inflammaging, an overactivation of immune response often resulting in aging.
Altered immune responses have been shown to manifest from age–related microbial dysbiosis, underlying a number of chronic health conditions. Similarly, the gut microbiota has emerged as a marker of aging, as highlighted in a 2022 review. Modulation of the gut microbiome, therefore, is imperative for regulation of epigenetic mechanisms.
The gut is dynamic, constantly shifting in response to diet, sleep, stress, and exercise. A varied, nutrient-dense diet rich in phytonutrients, fiber, and fermented foods supports GI health and microbial composition. Sleep quality and microbiome composition also have a bidirectional relationship, as demonstrated in a 2024 study published in Nutrients. Sufficient sleep is imperative for restoring microbial composition and integrity of the gut barrier, whereas poor sleep has been shown to impede these functions.
In fact, the gut microbiome exhibits its own circadian rhythm, underscoring this profound connection. More than half of the microbial mass of the gut microbiome has been shown to fluctuate throughout the day, having a rhythmic pattern. A 2023 study found that circadian rhythm can be disrupted by modern lifestyle—artificial light, jetlag, shift work, and eating around the clock can all induce disruptions in this system that modulates countless aspects of biological health. This concept is referred to as chrononutrition.
Regulating and mitigating stress is also essential, as it can impede microbial composition and integrity. Stress can further modify epigenetic mechanisms, as evidenced by a 2024 review published in Molecular Cell.
Gut microbiota live in close relationship with their host and have a profound role in genetic expression. By understanding and supporting the dynamic interplay between the gut microbiome and regulatory epigenetic mechanisms, we can optimize our health longevity. Nourishing ourselves, body and mind, is vital for favorably expressing our genes in restorative and beneficial ways.
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