PRJNA826978
Propionic acid protects ZnONPs-induced lung injury
Inhalation zinc oxide fumes results in the development of the clinical syndrome known as metal fume fever, the severe cases of which may develop to diffuse alveolar damage. However, the link between inhaled zinc oxide at nano-size (zinc oxide nanoparticles, ZnONPs)-induced acute lung injury (ALI) and intestinal microbiota remains largely unknown.To investigate the role and mechanism of intestinal microbiota and its metabolites short chain fatty acids (SCFAs) in the pathology of ZnONPs-induced ALI and the therapeutic potential of modulating intestinal microbiota in ZnONPs-induced ALI.Intratracheal instillation of ZnONPs was used to establish a ALI mice model; antibiotic cocktail treatment (ABX) and fecal microbiota transplantation (FMT) were used to modulate intestinal microbiota; 16S rRNA sequencing and LC-MS/MS were applied to evaluate the change of intestinal microbiota and SCFAs.Intratracheal instillation of ZnONPs caused macrophage-mediated ALI in mice. ABX-mediated depletion of intestinal microbiota aggravated ZnONPs-induced ALI; in contrast, FMT-mediated restoration of intestinal microbiota exerted opposite effects; ZnONPs inhalation resulted in the perturbation of intestinal flora and consequently the decrease of SCFAs (especial acetate acid or propionate acid) in the plasma; supplementation of sodium propionate, but not sodium acetate, remarkably ameliorated ZnONPs-induced ALI; GPR43 was the major receptor of propionate acid in RAW 264.7 macrophage cell lines. We illuminates a novel gut-lung axis mechanism that intestinal microbiota and its-derived metabolite propionate acid plays protective role against ZnONPs-induced ALI through repressing macrophage-mediated inflammation and oxidative stress via GPR43 receptor. FMT and supplementation of propionate acid are potential remedy strategies