# HS-Associated Pasteurella multocida Infection Disrupts Gut Microbiota and Metabolism in Mice

## TL;DR

This study shows that a respiratory infection in mice caused by a bacterium linked to hemorrhagic septicemia disrupts gut microbes and metabolism, highlighting a gut-lung connection.

## Contribution

The study reveals novel systemic effects of Pasteurella multocida infection on gut microbiota and tyrosine metabolism, emphasizing the gut–lung axis in septicemia.

## Key findings

- Respiratory infection with P. multocida NQ01 caused gut microbiota dysbiosis and reduced microbial diversity.
- Metabolomic analysis identified 1444 altered cecal metabolites, with significant disruption of tyrosine metabolism pathways.
- Key tyrosine pathway metabolites like L-tyrosine and dopamine were dysregulated, indicating metabolic breakdown.

## Abstract

Pasteurella multocida serotype B:2 is a primary agent of hemorrhagic septicemia (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 h post-infection, ileal tissues and cecal contents were collected for histopathological examination, 16S rRNA gene sequencing, 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 1444 significantly altered cecal metabolites, and pathway analysis indicated marked disruption of amino acid metabolism, notably the tyrosine metabolism pathway. Key tyrosine pathway metabolites were dysregulated (e.g., elevated L-tyrosine and dopamine with reduced L-DOPA), indicating a breakdown of this metabolic pathway. 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. multocida infection and offers a basis for exploring the gut–lung interaction in hemorrhagic septicemia pathogenesis.