Abstract
BACKGROUND: Comorbid allergic rhinitis and constipation (ARFC) in children are associated with gut microbiota (GM) dysbiosis and metabolic perturbations; however, the underlying mechanistic interplay remains unclear. OBJECTIVE: This multi-omics study aimed to characterize GM and fecal metabolomic signatures in preschool ARFC children and elucidate microbial-metabolite interactions driving dual symptomatology. METHODS: Fecal samples from 16 ARFC and 15 healthy control (HC) children underwent high-throughput absolute quantification 16S rRNA sequencing and untargeted metabolomics. Differential taxa and metabolites were identified via LEfSe and OPLS-DA (VIP > 1, false discovery rate (FDR) q < 0.05). Microbial-metabolite networks were reconstructed using genome-scale metabolic modeling and KEGG pathway analysis. RESULTS: The ARFC group exhibited distinct β-diversity (P = 0.031), marked by elevated Hungatella, Tyzzerella, and Bifidobacterium longum (P < 0.05). Metabolomics revealed upregulated aromatic amino acids (AAAs), neurotransmitters, and bile acids (FDR q < 0.05), with enrichment in tryptophan/tyrosine pathways (P < 0.01). Bioinformatic modeling linked Hungatella to tryptophan hydroxylase (EC:1.14.16.4), driving serotonin synthesis, and Tyzzerella to indoleamine 2,3-dioxygenase (EC:1.13.11.52), promoting kynurenine production. Bifidobacterium longum correlated with phenylalanine hydroxylase (EC:1.14.16.1), enhancing phenylalanine derivatives. A combined GM-metabolite diagnostic model demonstrated robust accuracy (AUC = 0.8). CONCLUSION: GM dysbiosis in ARFC children activates AAA metabolism, generating neuroactive and pro-inflammatory metabolites that may exacerbate allergic and gastrointestinal symptoms. These findings highlight microbial-metabolite axes as therapeutic targets. Study limitations include cohort size and lack of disease-specific controls, necessitating validation in expanded cohorts.