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.肠道菌群（gut microbiota）已被证实对呼吸道健康具有关键调控作用，但目前学界对其在呼吸道混合感染中的影响仍缺乏足够认识。本研究旨在利用小鼠模型，探究肠道菌群对涉及人畜共患病原体猪疱疹病毒1型（Suid herpesvirus 1, SHV-1）与多杀性巴氏杆菌（Pasteurella multocida, PM）的呼吸道混合感染的作用。研究结果显示，猪疱疹病毒1型感染会破坏小鼠肠道菌群平衡，加剧多杀性巴氏杆菌感染；该结论通过小鼠粪便样本的16S rRNA测序与粪便菌群移植实验得到验证。借助LEfSe分析发现，健康小鼠与感染病原体小鼠之间，毛螺菌科（Lachnospiraceae）是丰度发生显著变化的细菌科类。后续小鼠实验证实，口服毛螺菌科可有效缓解猪疱疹病毒1型诱导的多杀性巴氏杆菌感染。机制层面研究表明，口服毛螺菌科可修复猪疱疹病毒1型感染所破坏的呼吸道屏障完整性。此外，代谢组测序结果显示，口服毛螺菌科可恢复猪疱疹病毒1型感染后小鼠肠道中发生紊乱的多种代谢物（如琥珀酸钠、乙酸、丁酸等）。给小鼠施用这些代谢物可缓解感染相关症状并降低死亡率。本研究结果突显了“肠-肺轴（lung-gut axis）”在呼吸道感染中的重要作用。