Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection

Gut microbiome dysbiosis has been shown to alter the immune response to lung infection. Authors utilise a murine model to investigate if gut colonisation with carbapenemase-producing Enterobacterales altered the outcomes of Pseudomonas aeruginosa lung infection. Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.

Automated summary

Gut microbiome dysbiosis caused by carbapenemase-producing Enterobacterales (CPE) colonisation is associated with worsened outcomes of Pseudomonas aeruginosa lung infection in mice. The dysbiosis is characterised by decreased alveolar macrophages and conventional dendritic cells, as well as a decrease in the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and lung infection outcomes, indicating the involvement of CPE-induced gut dysbiosis in altering the gut-lung immune axis.