Butyrate remodels the immune-epigenetic-gut-lung axis: Emerging mechanisms and therapeutic perspectives in asthma.

Butyrate, a major microbial metabolite derived from dietary fiber fermentation, has emerged as a key regulator in the pathogenesis and treatment of asthma. It modulates the functions of dendritic cells, macrophages, and T cells, thereby reshaping the inflammatory microenvironment. In parallel, butyrate influences the transcriptional activity of inflammation-related genes through epigenetic mechanisms such as histone acetylation, DNA demethylation, and miRNA regulation. Notably, butyrate mediates long-range immune modulation via the gut-lung axis, linking intestinal microbial homeostasis to pulmonary inflammation. This review summarizes current advances in understanding the central role of butyrate within the immune-epigenetic-gut-lung network and discusses emerging therapeutic strategies based on microbiota modulation and targeted delivery systems. Regulation of the butyrate pathway offers new insights into the complex pathogenesis of asthma and potential avenues for innovative therapeutic development.