Article Impact Level: HIGH Data Quality: STRONG Summary of International Journal of Molecular Sciences https://doi.org/10.3390/ijms26178658 Dr. Noelle C. Rubas et al.
Points
- The gut microbiome significantly modulates host epigenetic mechanisms, including DNA and RNA methylation.
- Microbial presence actively reshapes host methylation profiles, influencing epigenetic regulator expression.
- Key pathways linking the microbiome to host epigenetics include one-carbon metabolism and short-chain fatty acids.
- Host factors like diet and aging reciprocally affect microbial composition and function within the gut.
- Understanding these interactions offers novel opportunities for precision health and therapeutic interventions.
Summary
This review comprehensively examines the intricate relationship between the human gut microbiome and host epigenomic reprogramming, particularly focusing on DNA and RNA methylation. The gut microbiome, a metabolically active and ecologically dynamic consortium, profoundly influences host physiology by modulating these epigenetic mechanisms, which in turn regulate gene expression and phenotypic plasticity. While evidence increasingly links microbial signals to host epigenetic changes, the precise molecular pathways remain incompletely understood. The review highlights recent discoveries, discussing evolutionarily conserved pathways through which gut microbiota regulate host methylation patterns, including one-carbon metabolism, polyamine biosynthesis, short-chain fatty acid (SCFA) signaling, and extracellular vesicle (EV)-mediated communication.
The reciprocal influence of host factors such as aging, diet, immune activity, and sociocultural context on microbial composition and function is also explored. Mechanistic insights include how microbial presence shapes host DNA and RNA methylation profiles; for instance, germ-free (GF) mice exhibit distinct methylomes compared to conventionally raised (CR) mice, with differences in gene expression and epigenetic regulator activity like DNMT3A and TET3. Liquid chromatography–mass spectrometry (LC-MS) analyses have also revealed distinct m6A RNA methylation profiles in various organs of specific pathogen-free (SPF) mice versus GF counterparts, indicating systemic microbial influence on epitranscriptomic marks.
Translational frontiers, such as biomarker discovery, live biotherapeutic interventions, fecal microbiota transplantation, and adaptive clinical trial designs, are outlined as potential avenues for microbiome-informed disease prevention and treatment. Advances in high-throughput methylation mapping, artificial intelligence, and single-cell multi-omics are accelerating the modeling of these complex interactions. Emphasizing rigorous standardization and ethical data governance, the review underscores that a deeper understanding of microbiome-host epigenome crosstalk offers novel opportunities for precision health strategies and equitable clinical translation, crucial for addressing conditions where altered epigenetic programs play a role.
Link to the article: https://www.mdpi.com/1422-0067/26/17/8658
References
Rubas, N. C., Torres, A., & Maunakea, A. K. (2025). The gut microbiome and epigenomic reprogramming: Mechanisms, interactions, and implications for human health and disease. International Journal of Molecular Sciences, 26(17), 8658. https://doi.org/10.3390/ijms26178658
