Gut microbial dysbiosis occurring during pulmonary fungal infection in rats is linked to inflammation and depends on healthy microbiota composition. Lung-gut axis in pulmonary infection

While the effect of gut microbiota and/or inflammation on a distant body site, including the lungs (gut-lung axis), has been well characterized, data about the influence of lung microbiota as well as lung inflammation on gut homeostasis (lung-gut axis) are scarce. Using a well-characterized model of pulmonary infection with the fungus Aspergillus fumigatus, we investigated alterations in the lung and gut microbiota by next generation sequencing of the V3-V4 regions of total bacterial DNA. Pulmonary inflammation due to the fungus A. fumigatus caused bacterial dysbiosis in both lungs and gut, but with different characteristics. While increased alpha diversity and unchanged bacterial composition were noted in the lungs, dysbiosis in the gut was characterized by decreased alpha diversity indices and modified bacterial composition. The altered homeostasis in the lungs allows the immigration of new bacterial species of which 41.8% were found in the feces, indicating that some degree of bacterial migration from the gut to the lungs occurs. On the other hand, the dysbiosis occurring in the gut during pulmonary infection was a consequence of the local activity of the immune system. In addition, the alteration of gut microbiota in response to pulmonary infection depends on the bacterial composition before infection, as no changes in gut bacterial microbiota were detected in a rat strain with diverse gut bacteria. The data presented support the existence of the lung-gut axis and provide additional insight into this mechanism.

尽管肠道菌群（gut microbiota）和/或炎症对包括肺在内的远端身体部位的影响（即肠-肺轴（gut-lung axis））已得到充分阐释，但关于肺菌群及肺部炎症对肠道稳态（gut homeostasis）的影响（即肺-肠轴（lung-gut axis））的相关数据仍较为匮乏。本研究采用经过充分验证的烟曲霉（Aspergillus fumigatus）肺部感染模型，通过对总细菌DNA的V3-V4区进行下一代测序（next generation sequencing），探究了肺与肠道菌群的变化情况。研究发现，烟曲霉引发的肺部炎症可导致肺与肠道均出现细菌生态失调（bacterial dysbiosis），但二者特征存在显著差异：肺部表现为α多样性（alpha diversity）升高且细菌组成无明显变化，而肠道生态失调则以α多样性指数降低、细菌组成发生改变为典型特征。肺部稳态失衡可允许新细菌物种定植，其中41.8%的新物种可在粪便中检出，这表明肠道与肺部之间存在一定程度的细菌迁移现象。另一方面，肺部感染过程中肠道出现的生态失调，是免疫系统局部活化的结果。此外，肺部感染引发的肠道菌群改变取决于感染前的肠道细菌组成：在肠道菌群多样性丰富的大鼠品系（rat strain）中，未检测到肠道细菌菌群的显著变化。本研究数据证实了肺-肠轴的存在，并为该轴的作用机制提供了新的科学见解。