Supplementary Material for: Airway microbiome composition and co-occurrence network are associated with inflammatory phenotypes of asthma

Introduction The composition and co-occurrence network of the airway microbiome might influence the asthma inflammatory phenotype. Airway microbiota change with asthma phenotypes, and the structure of the bacterial community in the airway might differ between different asthma inflammatory phenotypes and may also influence therapy results. Identifying airway microbiota can help investigate the role that microbiota plays in the asthma inflammatory process. Methods Induced sputum from 55 subjects and 12 healthy subjects from Beijing, China, was collected and analyzed for the bacterial microbiota. Microbiome diversity, composition, co-occurrence networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predicted and compared between the study groups. Results Significant differences in the sputum microbiome composition, co-occurrence network, and predicted functional pathways were observed between the two inflammatory phenotypes. Asthmatics in the low FeNO group exhibited lower α-diversity in the sputum microbiota and had higher abundance of the phylum Proteobacteria compared with that of the high FeNO group. Compared with the low FeNO group, the network in the high FeNO group was more “closed” and “connected”, and an alteration in the abundance of keystone species T. socranskii was found. Significantly different predicted metabolic subfunctions including nucleotide metabolism, lipid metabolism, energy metabolism, replication and repair, drug resistance antimicrobial and carbohydrate metabolism between the two studied phenotypes were also observed. Conclusion Our findings confirm that the airway microbiota is associated with the asthma inflammation process. The differences in the airway microbiome composition and co-occurrence network may affect distinct asthma inflammatory phenotypes. Our findings suggest the possibility that more targeted therapies could be applied based on the airway bacterial genera.

引言 气道微生物组的组成与共现网络或可影响哮喘炎症表型。气道菌群随哮喘表型发生变化，不同哮喘炎症表型患者的气道细菌群落结构可能存在差异，且该差异或会影响治疗效果。明确气道菌群特征，有助于探究菌群在哮喘炎症进程中的作用机制。方法 本研究收集了中国北京地区55名哮喘受试者与12名健康受试者的诱导痰样本，对其中的细菌菌群进行分析。对各组受试者的微生物组多样性、组成、共现网络以及京都基因与基因组百科全书 (Kyoto Encyclopedia of Genes and Genomes) 通路进行预测并开展组间比较。结果 本研究在两种炎症表型患者的痰微生物组组成、共现网络以及预测功能通路中均观察到显著差异。与高呼出气一氧化氮 (FeNO) 组哮喘患者相比，低FeNO组哮喘患者的痰微生物群α多样性更低，且变形菌门 (Proteobacteria) 的丰度更高。相较于低FeNO组，高FeNO组的菌群网络更为闭合且连通性更强，同时关键菌种T. socranskii的丰度发生了改变。两组研究表型间的预测代谢亚功能亦存在显著差异，涉及核苷酸代谢、脂质代谢、能量代谢、复制与修复、抗微生物药物耐药性以及碳水化合物代谢等通路。结论 本研究结果证实，气道菌群与哮喘炎症进程密切相关。气道微生物组组成与共现网络的差异或可影响不同的哮喘炎症表型。本研究结果表明，基于气道细菌属特征制定更具针对性的治疗方案具备潜在可行性。