Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis

<i>Klebsiella</i> (<i>K</i>.) <i>pneumoniae</i> is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in <i>K. pneumoniae</i>-infected mice and uninfected controls and showed that <i>K. pneumoniae</i> infection led to profound alterations in the gut microbiome and thus the cecal metabolome. We observed that the levels of <i>Lactobacillus reuteri and Bifidobacterium pseudolongum</i> were significantly decreased in <i>K. pneumoniae</i>-infected mice. Spearman correlation analysis showed that alterations in the richness and composition of the gut microbiota were associated with profound changes in host metabolite concentrations. Further, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, were detected in cecal contents and serum by gas chromatography-mass spectrometry (GC-MS). We observed that the concentrations of these three SCFAs were all lower in the infected groups than in the untreated controls. Lastly, oral supplementation with these three SCFAs reduced susceptibility to <i>K. pneumoniae</i> infections, as indicated by lower bacterial burdens in the lung and higher survival rates. Our data highlight the protective roles of gut microbiota and certain metabolites in <i>K. pneumoniae</i>-pneumonia and suggests that it is possible to intervene in this bacterial pneumonia by targeting the gut microbiota.