Gut microbiota-derived acetate mitigates Escherichia fergusonii-induced gut dysbiosis exacerbating Klebsiella pneumoniae pulmonary infection in mice

Escherichia fergusonii is an emerging food-borne opportunistic pathogen that disrupts gut homeostasis and exacerbates the severity of other organ diseases. However, the effects of gut colonization by E. fergusonii on the gut-lung axis remain unclear. Here we show that the abundance of Escherichia increases in microbiota-depleted mice and is enriches in patients with K. pneumoniae-associated pneumonia. Both alterations show a statistically significant correlation with the severity of lung infection. In the murine model, gut colonization by E. fergusonii induces specific gut dysbiosis, decreases intestinal and pulmonary acetate levels, and exacerbates carbapenem-resistant K. pneumoniae-induced pneumonia. Notably, fecal microbiota transplantation and acetate administration restore immune responses, ameliorate gut dysbiosis, increase acetate concentrations in intestinal and pulmonary tissues, and improve disease outcomes in mice with pneumonia. This study demonstrates that E. fergusonii-induced gut dysbiosis modifies the gut-lung immune axis in resistant K. pneumoniae-induced pneumonia and proposes a potential intervention strategy involving microbiota-derived acetate. Murine gut colonization modeling of E. fergusonii sheds light on this emerging opportunistic pathogen in disrupting the gut microbiota, reducing acetate levels, and exacerbating subsequent CRKPassociated pneumonia through the gut–lung immune axis.