Gut microbiota and the immune system: A regulatory axis through host MicroRNA modulation

The human gastrointestinal tract harbors trillions of microorganisms that collectively exert profound influences on host physiology, particularly immune function. Emerging evidence reveals that gut microbiota modulates immune responses through intricate interactions with host microRNAs (miRNAs), small non-coding RNAs that post-transcriptionally regulate gene expression. This review synthesizes current understanding of how gut bacteria influence host immunity via miRNA-dependent mechanisms. We examine two primary pathways: first, the capacity of gut microbes to regulate host miRNA expression profiles in immune cells and intestinal epithelium; second, the potential role of bacteria-derived small RNAs, including siRNA-like molecules, in potential cross-kingdom RNA communication (still under debate). Additionally, we explore the bidirectional nature of this interaction, whereby host miRNAs shape microbial composition and function. Comprehensive tables summarize disease-associated miRNA-microbe signatures and mechanistic pathways in immune regulation. The therapeutic implications of manipulating this axis through probiotics, dietary interventions, and miRNA-based therapies are discussed, along with future directions for translating these insights into clinical applications for inflammatory, autoimmune, and infectious diseases.