Abstract
Polyamines are ancient metabolites that serve critical functions in maintaining epithelial integrity, regulating immune response, and supporting healthy aging. The gut microbiota actively synthesizes and converts polyamines, while host factors such as inflammation, barrier function, and nutritional status dynamically modulate this metabolic network. Disruption of this host-microbiota axis reduces polyamine availability, impairs barrier function, and exacerbates inflammation. In contrast, polyamines exert protective effects by promoting epithelial repair, modulating macrophage and T-cell responses, and enhancing autophagy-mediated tissue renewal and longevity. Recent advances in engineered probiotics, microbial small RNAs, and postbiotics further highlight the therapeutic potential of precisely modulating polyamine metabolism in clinical contexts such as inflammatory bowel disease, metabolic syndrome, and neurodegenerative conditions associated with aging.