Antibiotic-induced microbiome depletion improves LPS-induced acute lung injury via gut-lung axis

Acute lung injury (ALI) is an acute inflammatory disorder. However, the precise mechanisms underlying the pathology of ALI remain elusive. An increasing evidence suggests the role of the gut-microbiota axis in the pathology of lung injury. This study aimed to investigate whether antibiotic-induced microbiome depletion could affect ALI in mice after lipopolysaccharide (LPS) administration.The effects of antibiotic cocktail (ABX) on ALI in the mice after intratracheally administration of LPS (5 mg/kg) were examined. Furthermore, 16s rRNA analysis and measurement of short-chain fatty acids in feces samples and metabolomics analysis of blood samples were performed.LPS significantly increased the interleukin-6 (IL-6) levels in the bronchoalveolar lavage fluid (BALF) of water-treated mice. Interestingly, an ABX significantly attenuated the LPS-induced increase in IL-6 in BALF and lung injury scores. Furthermore, ABX and/or LPS treatment markedly altered the α- and β-diversity of the gut microbiota. There were significant differences in the α- and β-diversity of the water + LPS group and ABX + LPS group. LEfSe analysis identified Enterococusfaecalis, Clostriumtertium, and Bacteroidescaecimyris as potential microbial markers for ABX + LPS group. Untargeted metabolomics analysis identified several plasma metabolites responsible for discriminating water + LPS group from ABX + LPS group. There were correlations between the relative abundance of the microbiome and plasma metabolites. Integrative network analysis showed correlations between IL-6 levels in BALF and several gut microbes (or plasma metabolites).These data suggest that ABX-induced microbiome depletion could protect against LPS-induced ALI via the gut-microbiota-lung axis.