Leptospirosis is a global natural zoonotic infectious disease.Research shows that short-chain fatty acids,metabolites of gut microbiota,are involved in host immune regulation and affect disease progression.This experiment was conducted to investigate the role of short-chain fatty acids in leptospirosis.The results showed that supplementation of short-chain fatty acid butyric acid could significantly improve the survival rate of leptospirosis in hamsters.In vitro experiments showed that butyric acid treatment inhibited the expression of Cat and Gsr genes in macrophages after infection with Leptospira,but enhanced the expression of NOX1 and NOX4 genes.At the same time,butyric acid treatment enhanced macrophage ROS levels after leptospirosis infection,and high levels of ROS enhanced the bactericidal function of macrophages.In vivo experiments al-so confirmed that butyric acid protects hamsters against acute leptospirosis by regulating ROS production.Collectively,the short-chain fatty acid butyric acid,a metabolite of gut microbiota,en-hances the bactericidal function of macrophages by regulating ROS expression,thereby protecting the host against leptospirosis.