# Glaesserella parasuis infection disrupts the gut–lung axis via microbiota dysbiosis and metabolic reprogramming leading to intestinal barrier impairment in piglets

## TL;DR

This study shows how a bacterial infection in piglets disrupts gut and lung microbes and metabolism, leading to intestinal damage.

## Contribution

The study reveals novel insights into how Glaesserella parasuis infection affects the gut-lung axis and intestinal barrier integrity in piglets.

## Key findings

- G. parasuis infection causes dysbiosis in both gut and lung microbiota.
- Metabolic changes include altered amino acid and xenobiotic metabolism.
- Infected piglets show intestinal barrier damage with elevated DAO and D-LA levels.

## Abstract

Glaesserella parasuis (G. parasuis), is a key respiratory pathogen responsible for Glässer's disease in pigs, characterized by polyserositis, arthritis, and pulmonary lesions. While it disrupts the respiratory microbiota, its impact on the gut-lung axis, a critical pathway for systemic immune and metabolic crosstalk, remains unexplored.

We established a piglet infection model using the highly virulent G. parasuis strain XX0306 (serotype 5). Systemic effects were investigated through integrated 16S rDNA sequencing of the lung and gut microbiota, complemented by untargeted metabolomics of intestinal contents. We performed histopathological examination and measured serum biomarkers (diamine oxidase and D-lactate) to assess intestinal barrier integrity. Correlation analysis linked microbial shifts to host metabolic alterations.

Infection induced profound dysbiosis in both the lung and gut microbiota. Pulmonary microbial diversity and functional potential declined. Gut dysbiosis featured a loss of beneficial bacteria and enrichment of potential pathogens (e.g., Streptococcus, Campylobacter, Desulfovibrio). Functional prediction indicated significant alterations in 12 gut microbial metabolic pathways, with downregulated amino acid metabolism and upregulated carbohydrate/lipid metabolism and xenobiotic degradation. Metabolomics identified 30 differentially abundant metabolites (e.g., argininosuccinate, liquiritigenin, citrulline), primarily enriched in cytochrome P450-mediated xenobiotic metabolism and arginine biosynthesis. Argininosuccinate levels correlated with pathogenic genera (Leucobacter, Streptococcus, Desulfovibrio). Infected piglets exhibited significant intestinal barrier damage, evidenced by elevated serum diamine oxidase (DAO) and D-lactate (D-LA).

This study demonstrates that G. parasuis infection extensively remodels the gut-lung axis microbiota and host metabolome, leading to intestinal barrier impairment. The perturbation of arginine biosynthesis may compromise host immunity. These results provide novel mechanistic insights into the pathogenesis of Glässer's disease.

Graphic illustrating the impact of *G. parasuis* infection in piglets on lung flora and gut-lung axis. Top section shows changes in microbial diversity, highlighting Proteobacteria and Firmicutes increase, while Cyanobacteria and Bacteroidetes decrease. The middle section describes the infection process, emphasizing the gut-lung connection. The bottom section details intestinal microbiota alterations and related metabolic pathways, including xenobiotic metabolism by cytochrome P450 and arginine biosynthesis. Various metabolites and bacteria influencing these processes are depicted.