Oral Lachnospiraceae plays a protective role in the host defense against respiratory herpesvirus infection and herpesvirus stimulated Pasteurella multocida infection

The gut microbiota has been identified as pivotal for respiratory health, yet there remains limited understanding of its influence on respiratory coinfection. This study aimed to explore the impact of the gut microbiota on respiratory coinfection involving the zoonotic pathogens Suid herpesvirus 1 (SHV-1) and Pasteurella multocida (PM) using mouse models. Our findings revealed that SHV-1 infection disrupted the balance of the murine gut microbiota, exacerbating PM infection in mice, as demonstrated by 16S rRNA sequencing of murine fecal samples and fecal microbiota transplantation experiments. Analysis using LEfSe identified Lachnospiraceae as a significantly altered bacterial family between healthy mice and those infected with the pathogens. Subsequent mouse studies demonstrated that oral Lachnospiraceae effectively ameliorated PM infection triggered by SHV-1. Mechanistically, oral Lachnospiraceae restored the integrity of the respiratory barrier disrupted by SHV-1 infection. Furthermore, oral Lachnospiraceae restored several metabolites (such as disodium succinates, acetic acids, or butyric acids) that were altered by SHV-1 infection in the murine gut, as revealed by metabolomics sequencing. Treatment of mice with these metabolites alleviated symptoms and reduced mortality associated with the infection. These findings underscore the significant role of the “lung-gut axis” in respiratory infections.