The HS-associated Pasteurella multocida Infection Disrupts the Gut Microbiota and Metabolism in Mice

Pasteurella multocida serotype B:2 is a primary agent of haemorrhagic septicaemia (HS) in livestock, and the strain NQ01 isolated from yaks highlights its cross-species impact. In this study, a murine intranasal infection model was established using P. multocida NQ01 to assess how acute respiratory infection perturbs gut homeostasis. Mice were intranasally inoculated with NQ01 and, at 36 hours post-infection, ileal tissues and cecal contents were collected for histopathological examination, 16S rRNA gene se-quencing, and untargeted metabolomic analysis. Histopathology revealed obvious acute bronchopneumonia but no overt ileal damage. However, 16S rRNA sequencing of cecal microbiota showed significant dysbiosis: microbial diversity was reduced and community composition shifted, including decreased short-chain fatty acid-producing taxa and increased opportunistic genera. Metabolomic profiling detected 1,444 significantly altered cecal metabolites, and pathway analysis indicated marked disruption of amino acid metabolism, notably the tyrosine metabolism pathway. Key tyro-sine-pathway metabolites were dysregulated (e.g., elevated L-tyrosine and dopamine with reduced L-DOPA), indicating a breakdown of this metabolic passway. These findings demonstrate that acute respiratory P. multocida infection profoundly disturbs gut microbiota and metabolism, underscoring disruption of the gut lung axis. This study provides new insight into the systemic consequences of HS-associated P. multo-cida infection and offers a basis for exploring the gut lung interaction in hemorrhagic septicemia pathogenesis.