article · Gut Microbes
Animals live alongside complex microbial communities that influence their development, immunity, metabolism, and behaviour. Beyond traditional metabolic and immune signalling, microbes regulate host gene expression through epigenetic mechanisms. These include alterations to DNA methylation, histone modifications, chromatin accessibility, and RNA pathways across various tissues. Findings across diverse animal models demonstrate that microbial regulation of host epigenetics is an evolutionarily conserved mechanism linking environmental signals to physical traits. Furthermore, these interactions occur within the tumour microenvironment, where intratumoural microbes may influence disease progression by remodelling epigenetic states. Microbial epigenetic regulation serves as a central regulatory interface across species, although important questions remain regarding the causality, cell-type specificity, persistence, and inheritability of these microbial-driven epigenetic effects.
Microbes inhabiting the body do not merely supply metabolites or activate immune responses; they actively change how host cells read their genetic code. Revealing how microbial signals alter epigenetic states provides a clearer framework for understanding how external environments shape animal development, long-term health, and diseases like cancer. This knowledge could fundamentally alter our understanding of host physiology.
This work represents early-stage fundamental research reviewing biological mechanisms across species. Understanding these pathways could eventually inform therapeutic development, particularly in manipulating microbial interactions within the tumour microenvironment or in treating immune and metabolic conditions. However, the abstract does not describe a tested technology, product, or applied development pathway, indicating the concepts are currently far from commercial deployment.
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Animals coexist with complex microbial communities that influence their development, immunity, metabolism, and behavior. Evidence shows these effects arise not just from metabolic and immune signaling but also from epigenetic mechanisms that alter host gene expression. Microbial signals can modulate DNA methylation, histone modification, chromatin accessibility, and RNA pathways, reshaping transcription across tissues. This review synthesizes evidence from diverse animal systems to demonstrate how microbial communities influence epigenetic landscapes and contribute to immunity, development, metabolism, and neurobiology. We explore data suggesting that microbial epigenetic interactions extend into the tumor microenvironment, where intratumoral microbes may shape disease progression by remodeling epigenetic states. Comparative studies indicate that microbial regulation of host epigenetics is an evolutionarily conserved mechanism linking environmental signals to phenotype. Despite recent advances, questions remain about causality, cell-type specificity, persistence, and inheritability of these effects. We propose microbial epigenetic regulation as a key interface integrating microbial cues with host physiology and pathology, providing a framework for understanding host-microbe interactions across species.
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DOI: 10.1080/19490976.2026.2725428
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