Arginine activates a conserved sphingolipid defense axis against infection

Metabolism is generally viewed as supporting immune responses rather than acting as a direct mediator of host defense. Here, we show that arginine directly activates the sphingolipid metabolic pathway in Plutella xylostella, promoting ceramide accumulation and consequently exerting antibacterial effects. Furthermore, we find that arginine synthesized by the host gut bacteria can activate this pathway, revealing an independent metabolic defense mechanism driven by gut bacterial arginine, which operates independently of classical immune cascades. Cross species validation shows that the ceramide biosynthesis pathway is highly conserved across eukaryotes, and its antipathogen effects display potential universality across insect species. This study opens new directions in gut innate immunity research, provides novel targets for the development of antimicrobial agents against insect pests, offers important reference value for eukaryotic pathology studies, and provides new insights into the development of novel therapeutic strategies against drug resistant bacterial infections.