The human body is an ecosystem consisting of different anatomical niches, such as the respiratory tract, gastrointestinal tract, and skin. Each microbial niche possesses its own physiochemical characteristics and is occupied by a specialised set of microbes [1]. The nasal cavity, nasopharynx, sinuses, and oropharynx shape specific microenvironments in the upper respiratory tract, which is constantly bathed in airflow from the external environment and exposed to atmospheric (physical and chemical) factors, including varying humidity, gases, immunological factors, and organic materials [2]. Nasal mucosa is the first-line defence against airborne pathogens [3]. These and other mucosae in the upper respiratory tract are colonised by specialised resident microbiota, presumably providing resistance to potential pathogens from establishing and disseminating towards the lungs, thereby functioning as gatekeepers to respiratory health [4]. Microbial communities throughout the nasal cavity and the upper respiratory tract typically form a continuum in community structure [3].

Nasal microbiota composition and function influence the susceptibility to respiratory illness, such as asthma [5,6,7], pneumonia [8,9], and chronic obstructive pulmonary disease [10,11]. Respiratory tract infections have also been identified as the most common reason for paediatric sick visits, antibiotic use, and health care expenditures during childhood [12,13,14]. Childhood asthma is the most common serious chronic respiratory disease in infants and children. The global prevalence, morbidity, mortality, and economic burden associated with this disease have sharply increased over the last 40 years [15].

Asthma is characterised by a range of respiratory symptoms including wheezing, coughing, shortness of breath, and chest tightness. The frequency and severity of its symptoms vary widely. Uncontrolled asthma and acute exacerbations may lead to respiratory failure [16]. Causes of asthma appear to be multifactorial but are commonly associated with genetics, living conditions, pathogenic infections of respiratory tract, nutrition, and others [17,18]. However, the mechanisms of asthma exacerbations remain poorly understood. Studies on asthma-related risk factors and pathogenesis would, therefore, aid in the effective prevention, diagnosis, and treatment of this disease.

Nasal microbial communities evolve rapidly during infancy and early childhood. Nasal health-associated commensal organisms (e.g., Corynebacterium, Dolosigranulum, and Staphylococcus lugdunensis) play essential functions in protecting hosts from respiratory tract infections [19,20]. Common nasopharyngeal opportunistic pathogens (e.g., Haemophilus (H.) influenzae, Streptococcus (S.) pneumoniae, and Staphylococcus (S.) aureus) can cause diseases when introduced into a susceptible body site or when hosts are immunologically compromised [21,22]. Nasal microbiota dysbiosis is characterized with altered compositions of bacterial species including increases in the number of pathogens and closely correlates with respiratory disease outcomes and overall health. Nasal microbiota dysbiosis not only significantly contributes to the morbidity of respiratory infections but also increases asthma risks and intensification during childhood [23].

The first two years of life are known as a particular window of health vulnerability. Upon delivery, including vaginal birth and caesarean section, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria [24]. Similar to other human body sites, the nasopharynx forms an ecological niche occupied by a variety of microbial species reflective of the delivery mode directly [24,25]. The most drastic changes occur during the first year of life and are probably driven by the maturation of the immune system [24]. Using 16S rDNA (V3–V5) sequencing, Mika et al. [26] identified the five most abundant bacterial families (Moraxellaceae, Streptococcaceae, Corynebacteriaceae, Pasteurellaceae, and Staphylococcaceae) in the nasal swabs of healthy infants in the first year of life, with relative abundances and composition varying with age and seasonal changes. In another study using 16S rDNA (V1–V3) sequencing, the five most highly represented genera, in the baseline nasal filter paper samples of healthy infants less than 6 months of age, were Corynebacterium, Streptococcus, Staphylococcus, Dolosigranulum, and Moraxella [27]. The formation of nasal microbial communities in early infancy is affected by host and environmental factors (e.g., mode, sex, age, and seasonality), and these factors have been found to correlate with the early onset of respiratory diseases such as acute respiratory infections (e.g., asthma and rhinitis) [28,29,30]. These findings indicate the potential role of early-life nasal microbiota homeostasis in maintaining nasal health.

Dysbiosis is defined as an imbalance or disruption of the microbial diversity, and the presence of a “dysbiotic” community in the airways may interact with epithelial and smooth muscle cells and cause asthma [31]. The microbial diversity is affected by various factors, such as drugs, surrounding environmental microorganisms, habitat, nutritional availability, host characteristics (e.g., hygiene, immunity, and genetics), physical factors (e.g., oxygen, pH, and moisture), and other microbial interactions [32]. The dysbiosis may happen in the upper or lower respiratory tract (or both). In the critical first year of life, nasopharyngeal microbiome composition is a determinant for infection spread to lower airways and risk of future asthma development [33].

A longitudinal study of Danish neonates (n = 321) using a culture-based method identified the pathogenic bacterial species Moraxella (M.) catarrhalis, S. pneumoniae, or H. influenzae in aspirates from the hypopharyngeal region in 21% (n = 66) of asymptomatic neonates at 1 month old [34]. During a 5-year prospective follow-up, the early presence of these pathogenic species increased the risk of wheezing, including a first wheezy episode, persistent wheezing, and hospitalisation for wheezing, as well as for subsequent diagnosis of asthma [34]. According to 16S rDNA (V4) sequencing, another longitudinal study of Australian infants (n = 234) demonstrated that the nasopharyngeal niche of most infants was initially colonised with Staphylococcus or Corynebacterium, which was replaced in a stepwise pattern by Corynebacterium, Alloiococcus, or Moraxella during the critical infancy period (≤12 months) [33]. Infants with acute respiratory infections (ARIs) were less colonised by Staphylococcus and Corynebacterium and more heavily colonised by Moraxella, Haemophilus, and Streptococcus. On the contrary, healthy infants were more colonised by Staphylococcus, Corynebacterium, and Alloiococcus. Notably, in nasopharyngeal aspirates collected before the first ARIs, a high Streptococcus abundance was more frequently detected in infants (≤9 weeks of age) who later displayed wheezing at 5 years of age than those did not. The same trend was also evident for wheezing at 10 years of age, indicating that Streptococcus was a potential wheezing-associated factor [33]. Using 16S rDNA (V4) sequencing, Toivonen et al. [35] identified four distinct longitudinal nasal microbiota profiles in the nasal swabs of a birth cohort of 704 children at ages 2, 13, and 24 months. The four microbial profiles were classified as persistent Moraxella dominance profile (with high Dolosigranulum and low Streptococcus and Staphylococcus abundances; 48%), Streptococcus-to-Moraxella transition profile (13%), persistent Dolosigranulum and Corynebacteriaceae dominance profile (24%), and persistent Moraxella sparsity profile (with persistently high Streptococcus and high Haemophilu as well as low Dolosigranulum abundances; 14%). The last profile of persistent Moraxella sparsity showed a significant association with a higher risk of asthma at age 7. By 16S rDNA (V4) sequencing, Tang et al. [36] showed that a Staphylococcus-dominant microbiome in nasopharyngeal mucus samples of infants in the first 6 months of life was associated with an increased risk of recurrent wheezing by age 3 years, persisted asthma throughout childhood, and early onset of allergic sensitization.

A case-control study used 16S rDNA (V3–V6) sequencing to analyse the nasal microbiota colonisation in infants with rhinitis and concomitant wheezing, with rhinitis alone and healthy controls (n = 122; ≤18 months) [28]. This study showed that five bacterial families (Corynebacteriaceae, Oxalobacteraceae, Moraxellaceae, Aerococcaceae, and Staphylococcaceae) dominated the nasal microbiota with an average summed abundance of 54.6%. Infants with rhinitis, particularly those who had wheezing concurrently, had nasal microbiome profiles different from those of healthy controls. Higher abundances of Oxalobacteraceae and Aerococcaceae and lower abundances of Corynebacteriaceae and Staphylococcaceae were observed in the rhinitis with wheezing group compared to the healthy control group. The significantly higher abundance of Oxalobacteraceae in patients with wheezing at an early age (up to 9 months) might also have promoted the early colonisation and increased number of Alloiococcus species, a common pathogen in otitis media [28].

Early nasal colonisation by Moraxella, Haemophilus, Streptococcus, and Staphylococcus has been significantly correlated with later chronic wheezing and asthma [33,35,36]. The initial establishment of Oxalobacteraceae might also be related to wheezing disorders and could be a predictive marker of subsequent increases in pathogen such as Alloiococcus [28]. Previous research findings imply that specific nasal bacterial exposures early in life can influence the development of asthma.

Respiratory syncytial virus (RSV) and rhinovirus (RV) are common, nearly universal, early-life infections. Infants are more likely to manifest immune responses to RSV and RV due to an immature immune system, predisposing them to possible chronic consequences of these severe infections. Early-life viral respiratory infections have been strongly linked to the development of childhood asthma [37,38]. Although there has been a long-standing debate regarding the causal relationship between infant viral respiratory infections and asthma risk, the type or pattern of nasal bacterial colonisation associated with asthma risk has been identified. Several studies have suggested that bacteria and viruses interact in maintaining health and influencing disease.

Lactobacillus abundance was associated with childhood wheezing illnesses in early life during RSV-ARI. Following RSV-ARI, infants with a high Lactobacillus abundance had a significantly reduced risk of wheezing compared to those with a low abundance of Lactobacillus at age 2 in a 2-year follow-up [38]. However, this finding may not be generalisable to infants without RSV-ARI as all subjects enrolled in this study were confirmed with RSV-ARI. In another child cohort study, M. catarrhalis and S. pneumoniae detected by quantitative real-time PCR in weekly nasal samples during RV infection were associated with increased asthma symptoms [39]. In a cohort study of American infants (n = 132) using 16S rDNA (V1–V3) sequencing, increased nasal abundances of Haemophilus, Moraxella, and Streptococcus and decreased abundances of Lactobacillus, Staphylococcus, and Corynebacterium were detected in infants with RSV-ARI when compared with healthy infants (average ≤ 6 months) during their first winter viral season [40]. Infants with more frequent RV infections had a lower Shannon diversity index [41], indicating that changes in the nasal microbiota associated with RV infections were characterized by a loss of microbial diversity. Persistent bacterial outgrowth occurred after viral infection, especially for the pathogen M. catarrhalis [34]. During wheezing illnesses, RV infection and the predominance of Moraxella at ages 2 and 3 were indicators of persistent childhood asthma [36]. These studies demonstrate that nasal microbiota colonisation and variations during early-life viral respiratory infection correlate with later respiratory health in childhood.

The distinction between commensal and pathogenic bacteria is often unclear, as some bacteria can be both commensal and opportunistic pathogens [42]. Nevertheless, the above studies have identified that the early presence of specific genera (Streptococcus, Moraxella, Haemophilus, and Staphylococcus) in nasal microbiota appears to be commonly associated with the development of respiratory diseases. For example, a high nasopharyngeal abundance of Streptococcus in early life is associated with an increased risk of wheezing and asthma in later childhood [33], and the presence of Oxalobacteraceae may serve as a predictor of early-onset wheezing [28]. Viral infection may drive the diversity variations of nasal microbiota and be associated with an increase in pathogens [34,41]. On the other hand, Lactobacillus may reduce the risk of subsequent wheezing in infants with a history of RSV-ARI [38].

The alteration in microbiota composition induced by pathological conditions leads to health issues. Previous studies have revealed changes in nasal microbial diversity and density with age and season. The alteration of nasal microbiota with age showed an increase in density and a decrease in diversity within the first year of life in healthy infants [26]. In contrast, another study comparing healthy infants and those with rhinitis showed that nasal microbial diversity increased in the former and decreased in the latter over the first 18 months of life [28]. Contradictory findings among studies may reflect that other contemporaneous life events in early infancy (e.g., changes in feeding patterns, antibiotics use, and childcare attendance) may have synergistic or inhibitory effects on colonisation of particular nasal microbiota.

A higher bacterial richness and specific bacterial profiles with more abundant Gram-negative α-proteobacteria and Gram-positive Bacilli were detected in the nasopharynx of summer-born asymptomatic neonates (1 month old) but not in those born in other seasons [43], indicating that birth season impacts the early colonisation of certain pathogens in the upper airways. Another study reported that peak colonisation occurred in fall/winter for M. catarrhalis and in winter/spring for H. influenzae via regular cycles of colonisation and clearance in healthy children [44]. The apparent increase in M. catarrhalis and H. influenzae detection in winter is likely a consequence of increased viral respiratory infections, such as influenza, resulting in increased opportunities for secondary infections by bacterial pathogens. McCauley et al. [45] collected nasal mucus samples from asthmatic children (ages 6 to 17) under steroid treatments during periods of respiratory health or first captured respiratory illness across all seasons. They observed that respiratory illnesses and exacerbations increased from late summer through late fall. In samples with first captured respiratory disease, higher relative abundances of multiple Moraxella taxa in spring and several Staphylococcus taxa in fall increased the risk of asthma exacerbation in a season-specific manner [45]. Several studies reported that infants with more than two respiratory tract infection episodes per year had an accelerated maturation rate of nasal microbiota [28,38,46], implying that respiratory tract infection may drive deviations from the ”normal” rate of the establishment of nasal microbiota.

The nasopharyngeal microbiome profiles in asthmatic children at 18 months of age were highly different compared to those of adults [47]. The nasopharyngeal microbiome at early childhood was dominated by the same six common genera from 2 months to 5 years, with a noticeable increase in within-sample α-diversity after 2 years of age in both healthy and ARI samples [48]. However, it had not yet reached the level of an adult-like nasopharyngeal microbiome, characterized by a much higher α diversity, lack of Moraxella and Corynebacterium, and less biomass [48,49].

Middle childhood (or the middle and late childhood; ages 6 to 12) is a stage where children move into expanding roles and environments, spending more time in school and other activities away from their family. Shifts in microbiota during this period occur due to changes in lifestyle, development of immunity, growth of bones, and so on [50,51]. The respiratory microbiota of middle-childhood children and adolescents (with ages of 6 to 18) with asthma partly overlapped with those of infants (<2 years) with respiratory infections [33,45,47,48,52]. By culture-based assessments, an earlier study reported that in healthy children (ages 2 to 9 years), the nostrils were enriched in Proteobacteria (Moraxella, Haemophilus, and Neisseria) and Firmicutes (Streptococcus, Dolosigranulum, Gemella, and Granulicatella), while in healthy adults, the nostrils were dominated by Actinobacteria (Corynebacterium, Propionibacterium, and Turicella) [53], indicating the striking differences in nasal microbiota composition between children and adults. In contrast, the gut microbiome matures to an adult-like state by 3 years of age [54]. The above findings indicate that the transition of respiratory microbiota communities toward a more adult-like configuration may take place over a longer period of childhood than that of other body compartments such as the gut. This may partly be the reason why many studies investigating the relationships between nasal microbiome and respiratory diseases did not categorize the participants into younger (ages 6 to 12) and older groups (ages 13 to 18) beforehand, even though the subjects recruited may cover a wide age range. However, we should notice that identification of the age of transition to an adult-like nasal microbiota by high-throughput sequencing assessments is needed for future studies, as this is a notable gap in current data.

A recent cross-sectional study by Pérez-Losada et al. [52] investigated the association of nasal microbiota with various phenotypes of childhood asthma using 16S (V4) rDNA sequencing. Asthmatic participants (n = 168, ages 6 to 18) were classified into three phenotypic clusters according to their clinical characteristics. The most abundant bacterial phylum (Proteobacteria) and pathogenic genus (Moraxella) associated with asthma varied significantly across different phenotypic clusters. The lowest abundances of these bacteria were detected in the group with the oldest mean age of asthma onset, mostly consisting of patients at risk of refractory asthma. The highest abundances were detected in the group with the youngest age of asthma onset, involving mainly patients with positive allergic asthma. Intermediate bacterial abundances were detected in the third group, involving the lowest proportion of subjects receiving positive allergy tests and subjects with the best outcomes for post-bronchodilator pulmonary function tests. This group might correspond to the best health outcomes. These findings reveal that the abundances of certain taxa are associated with particular paediatric asthma phenotypes. Asthma phenotypes with high and low abundances of specific bacteria, such as Proteobacteria and Moraxella, produced worse health outcomes than intermediate abundances of those bacteria.

By 16S rDNA (V1–V3) sequencing and metagenome shotgun sequencing, another cross-sectional study compared the composition of airway microbiota among healthy controls (n = 31), children with asthma (n = 31), and children with asthma in remission (n = 30) at around 8 years old [55]. The highest abundance of Staphylococcus was observed in the asthma group, and higher abundances of Streptococcus occurred in the two disease groups. These two bacteria might be more broadly negatively associated with lung function and bronchial hyperresponsiveness [55]. Studies have shown that differences in the diversity and abundance of nasal microbiota exist between asthmatic patients and healthy subjects and among different asthmatic phenotypes, indicating that specific microbiota alterations may contribute to asthma development and different clinical outcomes.

Longitudinal microbiome studies may help to uncover how shifts in microbiome profiles over time correspond to childhood asthma. Using 16S rDNA (V4) sequencing, a longitudinal study analysed the relationship between nasopharyngeal microbiota and ARIs in 244 children during their first 5 years of life [48]. Six genera (Moraxella, Streptococcus, Corynebacterium, Alloiococcus, Haemophilus, and Staphylococcus) remained dominant in the first five years of life. Although the within-sample α-diversity of the nasopharyngeal microbiota increased after 2 years of age for the remainder of the study period, Moraxella or both Alloiococcus and Corynebacterium appeared to be stable colonisers of the nasopharynx of healthy children. The asymptomatic colonisation of the upper airways by disease-associated taxa (Streptococcus, Haemophilus, and Moraxella) increased the risk of later chronic or transient wheezing (at 5 years old) [48]. This result was consistent with previous research showing that Streptococcus colonisation in early life is a risk factor for later childhood wheezing and asthma [33].

Changes in nasal microbiota over 5.5 to 6.5 months were studied in 40 asthmatic children (ages 6 to 18 years) using 16S rDNA (V4) sequencing by Pérez-Losada et al. [47]. Five genera (Moraxella, Staphylococcus, Streptococcus, Haemophilus, and Fusobacterium) dominated the nasopharyngeal core microbiome of these asthmatic children, with Moraxella and Streptococcus fluctuating more noticeably over time than the remaining genera.

Another study by McCauley et al. [56] collected weekly nasal secretion samples for 16 weeks from 413 asthmatic children (ages 6 to 17 years). In younger asthmatic children, asthma exacerbation was more strongly associated with Moraxella species-dominated microbiota, accompanied by a simultaneous rise in eosinophil activation. The nasal microbiota of children without asthma exacerbations were more likely to be dominated by Alloiococcus, Haemophilus, Corynebacterium, or Staphylococcus. Nasal microbiota dominated by Corynebacterium and Staphylococcus, observed in children who did not show exacerbations, were also associated with a generally decreased risk of respiratory diseases. Moraxella and Staphylococcus were the most frequently detected genera and exhibited the greatest temporal stability in the upper airways of asthmatic children over a 90-day observation period [56], which contradicted the aforementioned study by Pérez-Losada et al. [47]. Another study also revealed the association between variations in nasal, throat, and stool microbiota and asthma status among asthmatic children (n = 56, ages 3 to 17) [57]. Moraxella, Streptococcus, and Haemophilus predominated in all the samples from asthmatic patients under age 11. Within each site, the overall communities could not be distinguished during acute exacerbation and in the recovery phase, while nasal microbiota during these two periods were best associated with most of the clinical features (e.g., IgE level and dust mite allergy) compared with throat and stool microbiota. Nasal microbiota showed a higher diversity during acute exacerbation than the recovery phase, suggesting a more unstable and perturbed state presented during acute exacerbation. During acute exacerbation, the nasal microbiota of allergic children tended to be dominated by Corynebacterium and Dolosigranulum, which are often considered protective against acute exacerbation and have a positive role when the disease is under control. When moving into recovery, the relative abundance of Staphylococcus increased [57]. Hou et al. [58] investigated nasopharyngeal samples longitudinally at six time points (2- to 4-week intervals) from school-age asthmatic (categorizing into asthma exacerbation and stable asthma) and healthy children. They demonstrated that the nasopharyngeal microbiome underwent Moraxella expansion during asthma exacerbation and presented a high microbiome resilience (recovery potential) after asthma exacerbation. The relative abundances of Moraxella increased while Corynebacterium, Anoxybacillus, and Pseudomonas decreased longitudinally in all asthmatic samples. The longitudinal patterns of nasopharyngeal microbiome diversity and composition did not significantly differ between patients with asthma exacerbation and those with stable asthma. This result suggests that the short-term temporal dynamics of the nasopharyngeal microbiome cannot predict asthma exacerbation. Kloepfer et al. [39] longitudinally investigated nasal microbiota for five consecutive weeks during the peak RV season in autumn in children (ages 4 to 12) with current asthma (n = 166) and without asthma (n = 142). They found that the presence of RV alongside S. pneumoniae increased the frequency of exacerbations of asthma compared to weeks with no RV.

According to the findings of these longitudinal studies, genera such as Moraxella and Staphylococcus tended to dominate the nasal microbiota of asthmatic children stably [47,48,56,57]. Although Moraxella is a stable coloniser in children at almost all ages, its presence at a young age has been predictive of subsequent asthma exacerbation susceptibility [35,56,58]. In contrast to microbial communities in the throat and gut, nasal microbiota showed more obvious fluctuation during acute exacerbation of asthma [57]. Viral infections combined with bacterial colonisation may additionally increase the severity of respiratory diseases [37,39].

Both cross-sectional and longitudinal cohort studies have noted the variations in bacterial phyla and genera distribution in groups of asthmatic patients and healthy subjects or different asthmatic phenotypes. These studies have identified changes in nasal microbiota that may contribute to the development of asthma and the increased severity of asthmatic symptoms. However, studies that observe the variations in nasal microbiota in childhood asthma with larger sample sizes and more extended follow-up periods remain necessary to obtain more generalisable and reliable findings. Moreover, investigations focusing on the relationship between the nasal microbiome and subtypes of asthma could be a stepping stone for more detailed clinical application.