Multi-compartment microbial and metabolomic signatures are associated with acute asthma exacerbation in seasonal pollinosis: a nested matched case–control study

This nested matched case–control study, embedded in a prospective randomized controlled trial of Artemisia pollinosis prophylaxis, investigated available baseline nasal metabolomic and gut and nasal microbiomic profiles in a matched cohort of 64 patients with Artemisia pollen-induced rhinitis in relation to subsequent acute asthma exacerbation (AAE) during the pollen season. Participants were stratified into AAE (n = 32) and non-AAE (n = 32) groups and matched by prophylactic treatment, family allergy history, and Artemisia -specific IgE grade. Parallel profiling using 16S rRNA sequencing and untargeted metabolomics revealed group-associated microbial and metabolic signatures. The AAE group showed enrichment of several inflammation-associated taxa, whereas the non-AAE group retained multiple commensal-associated taxa. In the primary model containing baseline covariates only, fecal g__ Mesorhizobium was associated with AAE status (q = 0.0002), although its environmental origin and the absence of sequenced negative controls preclude exclusion of contamination. Nasal g__ Dolosigranulum met the exploratory q < 0.10 threshold (q = 0.068) and should not be regarded as a confirmatory finding. Metabolomic screening identified 128 features meeting the VIP, nominal p-value, and fold-change criteria after exclusion of 16 biologically implausible xenobiotic/drug annotations; none remained significant after Benjamini–Hochberg correction (q = 0.84186). These findings should therefore be considered exploratory, associative signatures that require independent validation.