Severity of acute lung injury in aspiration pneumonia model mice transplanted with human oral microflora

Objectives: When the microflora balance becomes disturbed, referred to as “dysbiosis,” immune homeostasis is altered, triggering various diseases. In the oral cavity, it is also becoming evident that dysbiosis can act as a stimulus for various systemic diseases. Aspiration pneumonia occurs when oral microflora enters the lungs of elderly individuals. Aspiration pneumonia is highly lethal and intractable; thus, a detailed understanding of the interaction between the microflora and lung immunity is essential to establish the optimal treatment. Methods: Human oral microflora-associated mice (HOMA) were created by transplanting human oral commensal microflora into germ-free mice. Then, the effects of oral microflora were analyzed on lung immunity and systemic conditions of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Results: The microflora in HOMA was in a state of dysbiosis. Furthermore, the accumulation of neutrophils in the lungs during septic conditions was more significant in HOMA. Serum tumor necrosis factor alpha (TNF-α) increased considerably in HOMA during ALI/ARDS. Simultaneously, the tissue distribution of lung macrophages in HOMA decreased more significantly in alveolar macrophages than in tissue macrophages. Finally, we found that microbial compositions in the lungs during ALI/ARDS were only a single or a small number of species, as in aspiration pneumonia in humans. Conclusion: Systemic inflammation and lung tissue damage were observed more significantly in HOMA during ALI/ARDS, suggesting that dysbiosis has a synergistic effect with septic shock, resulting in severe injury. Thus, oral and systemic dysbiosis may be a potential target for treating aspiration pneumonia in the elderly.