Airway microbial-microbial interaction plays an important role in chronic 22 airway inflammatory diseases such as asthma. Moraxella is widely regarded as a human respiratory tract pathogen. We aimed to investigate the interactions among Moraxella, 24 Moraxellaceae (to which Moraxella belongs) and the airway microbiome in asthma.Induced sputum samples were obtained from 116 asthma patients and 29 healthy 26 individuals, and the bacterial/fungal communities were profiled using 16S rRNA and ITS1 DNA gene sequencing. We found that asthma patients harboured significantly 28 greater airway bacterial and fungal α-diversity than that of healthy individuals. Moraxellaceae, Moraxella and Moraxella otu19 (bacteria), and Schizophyllaceae, 30 Polyporaceae, Aspergillus, Schizophyllum and Candida (fungi) were increased in the airway of asthma. Moreover, Moraxellaceae, Schizophyllaceae, Polyporaceae and 32 Candida were positively associated with airway fungal α-diversity. Correlation networks revealed Moraxellaceae and Moraxella as microbial "hubs" in asthma that had significant 34 negative connections with multiple bacterial communities, such as Leptotrichiaceae, Lachnospiraceae, Peptostreptococcaceae, Porphyromonadaceae, Prevotella, Veillonella, 36 Rothia and Leptotrichia, but positive interactions with fungal communities such as Schizophyllaceae, Polyporaceae, Candida and Meyerozyma. Together, our finding 38 revealed an altered microbiome and complex microbial-microbial interactions in the airway of asthma. Moraxellaceae and Moraxella showed significant interactions with the 40 airway mycobiome, providing potential insights into the novel pathogenic mechanisms of asthma.42 3 IMPORTANCE With the advent of culture-independent techniques, growing evidence suggests that the airway microbiome is closely correlated with chronic respiratory 44 diseases such as asthma. The complex microbial-microbial interaction exists in the airways of both healthy individuals and patients with respiratory diseases, which is of 46 great significance for the pathogenesis and disease progression of asthma. In this study, we evaluated the airway dysbiosis in asthma patients, described the interaction between 48 Moraxellaceae, Moraxella and airway bacterial/fungal communities, and it contributes to further understanding the pathogenic mechanisms of asthma. 50 KEYWORDS: asthma, airway microbiome, mycobiome, interaction, 16S rRNA, ITS 52 126 7 However, both the microbial α-diversity (Shannon index, bacteria: P=0.554, fungi:P=0.316, respectively) and β-diversity (bacteria: R 2 =0.009, P=0.269, fungi: R 2 =0.008, 128 P=0.549, respectively) were similar, and no significant differences in either bacterial or fungal community composition were found between the two subgroups ( Fig. S2).
130Although not statistically significant, the phylum that exhibited the greatest increase in asthma was Proteobacteria. We therefore evaluated the overall families belonging to 132 Proteobacteria. We found that the relative abundance of Moraxellaceae was significantly hig...
