Characteristics of airway microbiome co-occurrence network in patients with type 2 and non-type 2 asthma

Abstract

Objective: To study the characteristics of the airway microbiome co-occurrence network in patients with type 2 and non-type 2 asthma. Methods: In a prospective study based on a cohort of asthma patients, respiratory induced sputum samples were collected from 55 asthma patients [25 males and 30 females, with a median age of 47.7 years (age range 34.3-63.0 years)] admitted to the Department of Respiratory and Critical Care, Beijing Chaoyang Hospital, Capital Medical University and 12 healthy controls from the Physical Examination Centre of Beijing Chaoyang Hospital, Capital Medical University, from May 2021 to May 2022. According to the level of exhaled breath nitric oxide (FeNO), the asthma patients were divided into 22 cases in the high FeNO group (FeNO≥40 ppb, i.e., type 2 asthma group) and 33 cases in the low FeNO group (FeNO<40 ppb, i.e., non-type 2 asthma group). All induced sputum samples were subjected to second-generation macrogenomic sequencing and bioinformatic analyses of microbial community diversity, compositional characteristics, symbiotic network characteristics and metabolic function prediction. The Kruskal-Wallis rank sum test was used for between-group comparisons, and the linear discriminant analysis (LEfSe) method was used to compare the differences in flora composition between groups. The R language was used for microbial network analysis. In addition, PICRUSt was used to predict the metabolic-functional characteristics of the microbial communities. Results: The microbial communities in the healthy control group had a lower proportion of p_Firmicutes and p_Proteobacteria than asthma patients, 29% and 21%, respectively; 37% and 33% in the low FeNO group and 42% and 26% in the high FeNO group. The microbial network in the low FeNO group had 64 pairs of edges forming 16 communities, and about 75% of the nodes had eigenvector centrality values between 0 and 0.05, and 25% of the nodes had eigenvector centrality values between 0.10 and 0.45. There were four layers of κ-nucleosynthesis, and about 42% of the vertices were in the centre of the two layers. The microbial network of the high-FeNO group had 80 pairs of edges forming 18 clusters, and 81% of the nodes had eigenvector centrality values between 0 and 0.05, and 19% of the nodes had eigenvector centrality values between 0.10 and 0.35. The κ-nucleus decomposition had eight layers, and 21% of the vertices were located in the centre's two layers. The main functional differences between the low and high FeNO groups were shown in metabolic pathways (including sugar, lipid, amino acid, and energy metabolism), drug resistance, biofilm transport, signalling, intercellular communication, and cellular repair. Conclusions: Compared with non-type 2 asthmatics, type 2 asthmatics had a higher alpha diversity of respiratory microbiota, lower levels of microorganisms in the p_Proteobacteria, and a more aggregated microbial network. There was a significant difference in the predicted metabolic function of the two endotypes of asthmatics.