Abstract N 6 ‐methyladenosine (m 6 A) is the most prevalent posttranscriptional modification in eukaryotic mRNAs. Dynamic and reversible m 6 A modification regulates gene expression to control cellular processes and diverse biological functions. Growing evidence indicated that m 6 A modification is involved in the homeostasis of host and microbes (mostly viruses and bacteria). Disturbance of m 6 A modification affects the life cycles of viruses and bacteria, however, these microbes could in turn change host m 6 A modification leading to human disease including autoimmune diseases and cancer. Thus, we raise the concept that m 6 A could be a “messenger” molecule to participate in the interactions between host and microbes. In this review, we summarize the regulatory mechanisms of m 6 A modification on viruses and commensal microbiota, highlight the roles of m 6 A methylation in the interaction of host and microbes, and finally discuss drugs development targeting m 6 A modification. This article is categorized under: RNA in Disease and Development > RNA in Disease