Fragmented gut-airway microbial networks and airway Moraxella clusters in preschool wheeze

Early-life wheezing in children has been associated with microbial alterations along the gut-airway axis, yet studies simultaneously investigating bacterial communities in both compartments remain scarce. The aim of this cross-sectional exploratory pilot study (n=25) was to characterize and compare nasal and stool bacterial communities in preschool children aged 1-4 years with recurrent wheezing and healthy controls using 16S rRNA gene metabarcoding. Across participants, nasal and stool bacteriomes were highly individualized and taxonomically diverse. Overall richness, evenness, and community composition did not differ significantly between healthy children and wheezers in either compartment. However, wheezers displayed markedly higher within-group variability, particularly in nasal communities. Stratification based on microbiome similarity to healthy samples revealed increased Moraxella and reduced commensal genera including Prevotella spp. and Veillonella, along with lower richness and evenness (all p<0.001) in nasal samples with divergent bacterial communities. Stool alterations were more subtle but included trends toward reduced Bacteroides, Faecalibacterium, and Alistipes in wheezers more divergent from healthy controls. Community assembly in both compartments was largely governed by stochastic processes but accompanied by less complex and more fragmented bacterial interaction networks in wheezing children. Cross-compartment correlations were also altered, most prominently involving stool Lactococcus showing stronger and more numerous correlations with nasal taxa in wheezers than in healthy controls. Divergent wheezers exhibited distinct modular network structure and cross-compartment profiles, consistent with a differentiated microbial organization. Together, these findings suggest compartment-specific differences in microbial interaction patterns across the gut-airway axis in early-life wheezing, despite limited differences in overall community diversity. Take home messagePreschool wheezers showed fragmented gut-airway microbial networks and Moraxella-associated airway community stratification despite limited differences in overall diversity.