Associations of indoor bacterial, metabolomic, and other chemical exposures with allergic rhinitis in school-aged children

BACKGROUND: The indoor environment has been implicated as a critical factor in the development of allergic diseases. However, the interplay among indoor microbiota, metabolites, and other environmental chemicals in relation to childhood allergic rhinitis (AR) remains underexplored, particularly in subtropical regions. This study investigates the joint associations of multi-omics profiles in classroom dust with AR prevalence among school-aged children in southern China. METHODS: This cross-sectional study was conducted in 2023 across 45 middle schools in Guangzhou, China, encompassing 3,944 students. Classroom dust was analyzed using 16S rRNA gene sequencing for bacterial community profiling and untargeted UHPLC-MS/MS for small-molecule compound profiling (including metabolites and environmental chemicals). Classrooms were stratified into high- and low-AR prevalence groups based on the median AR prevalence. Multivariate statistics, machine learning (random forest with SHAP), and interaction analysis were employed to compare bacterial communities and compound profiles between the two groups and to examine the joint effects of bacterial-compound pairs on AR prevalence. RESULTS: Significant differences in bacterial β-diversity were observed between high- and low-AR prevalence classrooms (PERMANOVA, p < 0.05). At the genus level, low-AR prevalence classrooms were enriched with environmental bacteria including Pseudorhodoferax, Cupriavidus, Enterobacter, and Marmoricola, whereas high-AR prevalence classrooms showed higher relative abundances of Sutterella, Tannerella, Bifidobacterium, Fusobacterium, Bacteroides, and Lawsonella. A total of 395 small-molecule compounds were differentially abundant between groups (variable importance in projection [VIP] > 1, p < 0.05), of which 239 were elevated in high-prevalence classrooms and 156 in low-prevalence classrooms. Interaction analysis revealed a significant signal intensity-dependent interaction between Tannerella and the oxidized ceramide Cer(d17:1/6 keto-PGF1alpha) (FDR = 0.002): Tannerella was positively associated with AR prevalence at low ceramide levels but negatively associated at high levels. CONCLUSIONS: Classroom bacterial community composition and small-molecule compound profiles are associated with AR prevalence among school-aged children in subtropical South China. Specific environmental compounds can substantially modify the direction of the association between bacteria and AR, highlighting the need to move beyond traditional diversity-based approaches and integrate multi-omics data to identify modifiable environmental exposure risks.