Faecal Microbiota Transplantation in IL-10 Knockout Mice Reverses Increased Susceptibility to Pseudomonas aeruginosa Lung Infection

Abstract

Differences in the gut microbiota are directly reflected in lung–gut axis crosstalk, which may increase susceptibility to pulmonary infections, such as those caused by the bacterium Pseudomonas aeruginosa. Deficiency of the cytokine IL-10 leads to gut inflammation, and this pro-inflammatory environment is partly due to changes in the gut microbiota. To better understand the effects of IL-10 deficiency on the gut microbiota, the intestinal microbial composition of IL-10 KO mice was assessed, and an increase in the phyla Bacteroidetes and Proteobacteria and a decrease in the phylum Firmicutes were observed in the faeces compared with the wild-type group (WT). Additionally, IL-10 KO mice had a higher pro-inflammatory immunostimulatory caecal content. Furthermore, it was found that heterologous faecal microbiota transplantation (FMT) between groups reversed this gut imbalance. IL-10 KO mice showed greater susceptibility to acute pulmonary infection by P. aeruginosa, with a higher recovery of viable bacteria in the lung and spleen, greater tissue damage and increased expression of genes encoding pro-inflammatory cytokines in the lungs. This greater susceptibility was reversed after FMT. Taken together, these results demonstrate the role of endogenous IL-10 in the gut microbiota constitution and its importance in the pulmonary immune response against P. aeruginosa infection.