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

• Published in: Life sciences (1973) 2022-10, Vol.307, p.120885-120885, Article 120885
• Main Authors: Hashimoto, Yaeko, Eguchi, Akifumi, Wei, Yan, Shinno-Hashimoto, Hiroyo, Fujita, Yuko, Ishima, Tamaki, Chang, Lijia, Mori, Chisato, Suzuki, Takuji, Hashimoto, Kenji
• Format: Article
• Language: English
• Subjects: Acute lung injury; ARDS; LPS; Lung-gut axis; Microbiota
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120885

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. Some materials in the graphical abstract were designated using resources from www.irasutoya.com. [Display omitted]