The association of airway microbiota with allergen sensitization and allergic airway diseases has not been well determined so far. This study demonstrated that the existence of an inverse association between airway microbial diversity and sensitization to house dust mites. Dysbiosis of particular subsets of the airway microbiota may take part in allergic reactions in response to allergen exposure, which can potentially cause susceptibility to rhinitis and asthma in early childhood.

Microbes associated with humans play an essential role in immunity and health, and microbial community composition has been linked with several different diseases13, 14. The first study to examine airway microbiota using culture-independent techniques revealed that airways are not sterile and possess their own specific microbiota15. Although the dispersal of oral commensals has been shown to be the dominant source of organisms shaping airway microbiota, the composition of the lower airway microbiome does not derive entirely from the oral cavity15, 16. Despite this, the oropharynx is constantly exposed to microbes from both the upper and lower respiratory tract, where may represent the microbes related to airway diseases including allergic rhinitis and asthma17, 18.

Several studies have reported associations between gross metrics of bacterial community composition and asthma19. In allergy and asthma, a reduced airway microbial diversity has been hypothesized to increase the risk of allergic manifestations20. As in this study, a relatively lower bacterial richness and diversity in the airways was found in children with childhood rhinitis and asthma than in the healthy controls. However, the bacterial diversity colonizing the airways has been found to be greater in adult asthmatic compared with healthy subjects21. Although this inconsistency may be a result of differences in sampling site, age, and the spectrum of disease severity in the study populations, this discrepancy highlights potential differences in airway microbiota affecting asthma between adults and children.

The upper respiratory tract is considered the point of entry for aeroallergens and commensal bacteria into the airways through microaspiration18. Exposure and sensitization to allergens are the most important risk factors for the development of allergic airway diseases22. Bacterial exposure has been reported to modulate immunity to against atopic asthma by suppressing Th2 immune responses, which are related to allergic reactions in response to allergens23. In this study, low airway microbial diversity appeared to be associated with increased mite sensitization. In addition, it was also found to be lower in mite-sensitized children with rhinitis and asthma than in healthy children without mite sensitization. These findings suggest alterations in airway microbiota induce or suppress systemic immune tolerance to inhalant antigens, which may be attributed to the link between the microbiota composition and atopic disease.

The diversity of microbial species, rather than exposure to one particular microbial component, is particularly protective24. However, exposure to different types of bacteria may have different effects in allergic diseases. In this study, members of the phylum Proteobacteria, including the genera Haemophilus, Neisseria, and Moraxella, were found numerically to be more abundant in the airways of children with rhinitis than in the healthy controls. Clinically, these bacteria are the most common pathogens in acute and chronic sinusitis and otitis media, which are usually complicated by poorly controlled symptoms of allergic rhinitis25. In particular, the genus Moraxella has been shown to be involved in the interaction between mite sensitization and rhinitis, suggesting that Moraxella spp. may not only contribute to poor rhinitis control, but also play a role in modulating allergen sensitization that is involved in allergic rhinitis.

Despite a significant relationship between microbiota and asthma, no particular subsets of the microbiota have been consistently found to be associated with asthma. Neisseria species have been identified to be abundant in asthmatics and related to the degree of eosinophilic inflammation26. In this study, Neisseria spp. were found to be more abundant in children with rhinitis but not asthma without association with allergen sensitization. The presence of members of the phylum Bacteroidetes, especially Prevotella spp., in the airways has been reported to be protective against asthma in older children and adults15. However, in this study, Prevotella spp. was found to be significantly associated with sensitization to house dust mites but not rhinitis or asthma. Similarly to Prevotella spp., Butyrivibrio spp. and Selenomonas spp. appeared to be associated with asthma because of their strong association with mite sensitization. These results indicate that a modulation between microbial dysbiosis and responses to allergens in the airways may potentially cause differences in susceptibility to childhood rhinitis and asthma.

Leptotrichia species are typical anaerobic, gram-negative bacilli, which are primarily part of the normal flora in the mouth. In this study, Leptotrichia spp. were not only strongly associated with mite sensitization but were also linked with asthma. In particular, Leptotrichia spp. appeared to be more abundant in children without mite sensitization, supporting the results from one other birth cohort study that reported an inverse association between the abundance of gram-negative bacteria and allergic sensitization27. Although the clinical importance of Leptotrichia spp. remains unclear, the involvement of Leptotrichia spp. in immune responses to allergens may particularly explain the pathogenesis of asthma in early childhood.

One major limitation of this study is a relatively small sample size resulting limited statistical power for the subanalyses. Furthermore, this study’s relatively short follow-up period may make the diagnosis of subclinical atopy be missed. The presence of diverse microorganisms across different sites and the dissimilarities in microbial compositions in a wide range of age groups are two common limitations for microbiome analysis. The strength of the present study, however, lies in its accurate sample collection performed by the same physician for a consistent sampling site. A comparison of the microbiota in children with a very small age difference also makes our results valid and potentially important.

In conclusion, the analysis of airway microbiota provides new insights into its pathogenic potential and implication on health and in allergic airway diseases. The microbial diversity in airways appears to be inversely associated not only with allergen sensitization, but also with rhinitis and asthma in mite-sensitized children, indicating that the interactions between airway microbiota and allergic reactions in response to allergen exposure may play an important role in allergic airway diseases. Moraxella spp. and Leptotrichia spp. were found to significantly contribute to this interaction, suggesting that a modulation between particular subsets of airway dysbiosis and allergen responses could potentially cause susceptibility to rhinitis and asthma. Further studies with functional analysis, however, are required to investigate these associations more comprehensively.