National Heart and Lung Institute, Imperial College London, London, UK.
Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.
Commun Biol. 2024 Feb 12;7(1):171. doi: 10.1038/s42003-024-05840-3.
Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.
气道黏膜屏障的微生物群落具有保守性和高度有序性，很可能反映了与人类宿主因素的共同进化。由于不需要选择来消化营养物质，气道微生物组为黏膜免疫和病原体抗性的同源管理提供了基础。我们在这里展示了对胸气道细菌进行系统培养和全基因组测序的初步结果，在构成健康个体中通常存在的 75%共生体的 126 种生物体中，鉴定出了 52 种新物种。临床相关基因编码抗菌合成、黏附和生物膜形成、免疫调节、铁利用、一氧化二氮（NO）代谢和鞘脂信号转导。我们利用全基因组内容鉴定了可能影响哮喘和慢性阻塞性肺疾病的失调特征。我们将分离株的基因内容与气道上皮细胞分化后期表达的转录本和代谢物进行匹配，确定了维持宿主与微生物群相互作用的途径。我们的研究结果为解析在具有全球意义的肺部疾病中共生体、病原体和黏膜之间的相互作用提供了系统的基础。
