1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and.
2 Michigan Center for Integrative Research in Critical Care, Ann Arbor, Michigan; and.
Am J Respir Crit Care Med. 2018 Aug 15;198(4):497-508. doi: 10.1164/rccm.201711-2180OC.
The "gut-lung axis" is commonly invoked to explain the microbiome's influence on lung inflammation. Yet the lungs harbor their own microbiome, which is altered in respiratory disease. The relative influence of gut and lung bacteria on lung inflammation is unknown.
To determine whether baseline lung immune tone reflects local (lung-lung) or remote (gut-lung) microbe-host interactions.
We compared lung, tongue, and cecal bacteria in 40 healthy, genetically identical, 10-week-old mice, using 16S ribosomal RNA gene quantification and sequencing. We measured inflammatory cytokines, using a multiplex assay of homogenized lung tissue. We compared lung bacteria in healthy mice treated with varied durations of systemic antibiotics.
Lung bacterial communities are highly variable among mice, cluster strongly by cage, shipment, and vendor, and are altered by antibiotics in a microbiologically predictable manner. Baseline lung concentrations of two key inflammatory cytokines (IL-1α and IL-4) are correlated with the diversity and community composition of lung bacterial communities. Lung concentrations of these inflammatory cytokines correlate more strongly with variation in lung bacterial communities than with that of the gut or mouth.
In the lungs of healthy mice, baseline innate immune tone more strongly reflects local (lung-lung) microbe-host interactions than remote (gut-lung) microbe-host interactions. Our results independently confirm the existence and immunologic significance of the murine lung microbiome, even in health. Variation in lung microbiota is likely an important, underappreciated source of experimental and clinical variability. The lung microbiome is an unexplored therapeutic target for the prevention and treatment of inflammatory lung disease.
“肠-肺轴”通常被用来解释微生物组对肺部炎症的影响。然而，肺部本身也拥有其微生物组，而在呼吸系统疾病中，肺部微生物组会发生改变。肠道和肺部细菌对肺部炎症的相对影响尚不清楚。
确定基线肺部免疫反应是否反映局部（肺-肺）或远程（肠-肺）微生物-宿主相互作用。
我们使用 16S 核糖体 RNA 基因定量和测序技术，比较了 40 只健康、遗传相同、10 周龄的小鼠的肺部、舌部和盲肠细菌。我们使用肺部组织匀浆的多重分析测定法测量了炎症细胞因子。我们比较了接受不同持续时间全身抗生素治疗的健康小鼠的肺部细菌。
肺部细菌群落之间在小鼠之间差异很大，按笼子、运输和供应商聚类很强，并且抗生素以微生物学上可预测的方式改变。两种关键炎症细胞因子（IL-1α和 IL-4）的基线肺部浓度与肺部细菌群落的多样性和群落组成密切相关。这些炎症细胞因子在肺部的浓度与肺部细菌群落的变化相关性更强，而与肠道或口腔的变化相关性较弱。
在健康小鼠的肺部，基线先天免疫反应更强烈地反映了局部（肺-肺）微生物-宿主相互作用，而不是远程（肠-肺）微生物-宿主相互作用。我们的结果独立证实了健康小鼠肺部微生物组的存在及其免疫学意义，即使在健康状态下也是如此。肺部微生物组的变异性可能是实验和临床变异性的一个重要但未被充分认识的来源。肺部微生物组是预防和治疗炎症性肺部疾病的一个未被探索的治疗靶点。
