Rubas Noelle C, Torres Amada, Maunakea Alika K
Department of Molecular Bioscience and Bioengineering, University of Hawai'i at Mānoa, Honolulu, HI 96822, USA.
Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI 96822, USA.
Int J Mol Sci. 2025 Sep 5;26(17):8658. doi: 10.3390/ijms26178658.
The human gut microbiome is a metabolically active and ecologically dynamic consortium that profoundly influences host physiology, in part by modulating epigenetic mechanisms such as DNA and RNA methylation. These modifications regulate gene expression and phenotypic plasticity and are shaped by a combination of environmental factors, such as diet, stress, xenobiotics, and bioactive microbial metabolites. Despite growing evidence linking microbial signals to host epigenetic reprogramming, the underlying molecular pathways remain incompletely understood. This review highlights recent mechanistic discoveries and conceptual advances in understanding microbiome-host epigenome interactions. We discuss evolutionarily conserved pathways through which gut microbiota regulate host methylation patterns, including one-carbon metabolism, polyamine biosynthesis, short-chain fatty acid signaling, and extracellular vesicle-mediated communication. We also examine how host factors such as aging, diet, immune activity, and sociocultural context reciprocally influence microbial composition and function. Beyond basic mechanisms, we outline translational frontiers-including biomarker discovery, live biotherapeutic interventions, fecal microbiota transplantation, and adaptive clinical trial designs-that may enable microbiome-informed approaches to disease prevention and treatment. Advances in high-throughput methylation mapping, artificial intelligence, and single-cell multi-omics are accelerating our ability to model these complex interactions at high resolution. Finally, we emphasize the importance of rigorous standardization and ethical data governance through frameworks such as the FAIR and CARE principles. Deepening our understanding of how the gut microbiome modulates host epigenetic programs offers novel opportunities for precision health strategies and equitable clinical translation.
人类肠道微生物群是一个代谢活跃且生态动态的群落，它深刻影响宿主生理，部分是通过调节诸如DNA和RNA甲基化等表观遗传机制来实现的。这些修饰调节基因表达和表型可塑性，并由饮食、压力、外源性物质和生物活性微生物代谢产物等环境因素共同塑造。尽管将微生物信号与宿主表观遗传重编程联系起来的证据越来越多，但潜在的分子途径仍未完全了解。本综述重点介绍了在理解微生物群-宿主表观基因组相互作用方面的最新机制发现和概念进展。我们讨论了肠道微生物群调节宿主甲基化模式的进化保守途径，包括一碳代谢、多胺生物合成、短链脂肪酸信号传导和细胞外囊泡介导的通讯。我们还研究了衰老、饮食、免疫活性和社会文化背景等宿主因素如何相互影响微生物组成和功能。除了基本机制，我们概述了转化前沿——包括生物标志物发现、活体生物治疗干预、粪便微生物群移植和适应性临床试验设计——这些可能使基于微生物群的疾病预防和治疗方法成为可能。高通量甲基化图谱、人工智能和单细胞多组学的进展正在加速我们以高分辨率模拟这些复杂相互作用的能力。最后，我们强调通过诸如FAIR和CARE原则等框架进行严格标准化和道德数据治理的重要性。加深我们对肠道微生物群如何调节宿主表观遗传程序的理解，为精准健康策略和公平的临床转化提供了新的机会。
