How microbes reprogram immunity through epigenetic and epitranscriptomic regulation.

Microbial signals are linked to stable immune cell state changes through interconnected epigenetic and epitranscriptomic regulation, with the microbiota–N6-methyladenosine (m6A) axis highlighted across compartments.

• Why it matters: It remains unclear how transient microbial cues become durable, reversible, or disease-promoting immune programs, limiting mechanistic understanding of host–microbiota control of immunity.
• What they did: This review synthesizes evidence that microbial antigens, structural ligands, and metabolites engage chromatin- and RNA-regulatory pathways in epithelial, myeloid, lymphoid, and stromal compartments, emphasizing RNA modification biology including m6A.
• The result: The framework explains how the same microbial molecule can be associated with barrier repair, immune tolerance, inflammation, or antitumor immunity depending on tissue exposure, cell type, and host state, while calling for studies on non-m6A modifications and bidirectional regulation.

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