Key messengers in the gut-nose axis: mechanisms of gut microbial metabolites in the immunomodulation of allergic rhinitis

Allergic rhinitis (AR) is a common clinical chronic inflammatory respiratory disease, in which immune imbalance serves as a core component of its complex pathogenesis. In recent years, the gut-nose axis has emerged as a novel pathway mediating immune crosstalk between the intestinal tract and the nasal cavity, garnering significant academic attention. Gut microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines) are profoundly involved in the pathophysiology of AR by reshaping the nasal mucosal immune microenvironment via systemic circulation and neural pathways and regulating the Th2/Treg balance, innate lymphoid cells (ILC2s), and mast cell functions. This article systematically reviews the immunomodulatory mechanisms of core gut microbial metabolites, explores their impact on nasal mucosal epithelial barrier function and immune cell activity, and summarizes metabolite-based clinical intervention strategies, including postbiotic therapy (bioactive compounds derived from microbial cells or metabolites), precision nutritional interventions, and fecal microbiota transplantation. Additionally, the paper analyzes current challenges such as heterogeneity and dose-response effects, aiming to provide a theoretical foundation for understanding the immunomodulatory mechanisms of the gut-nose axis and a reference for developing novel precision strategies for the prevention and treatment of AR.