Ethnopharmacological relevancePerturbations in airway microbiota composition and disruption of microbe-metabolite interactions have been observed in respiratory infectious diseases (RIDs). The Yinhuang (YH) buccal tablet, as an ancient Chinese medicinal formula, has been traditionally employed for the management of upper RIDs. However, there is a lack of evidence for the effects of YH buccal tablets on upper respiratory tract microbiota and circulating metabolites. Aim of the studyThe aim of this study was to analyze the changes in respiratory microbiota composition and circulating metabolite profile after YH buccal tablets administration. Materials and methodsThroat swab samples and serum samples were collected from 60 healthy subjects for high-throughput 16S ribosomal RNA gene (16S rRNA) sequencing and non-targeted Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. ResultsAirway microbial composition changed significantly after YH administration. The abundance of Actinomyces and Prevotella_7 increased, while the abundance of potentially pathogenic Pseudomonas and Corynebacterium decreased. A total of 168 significant HMDB taxonomic metabolites were identified in serum samples, of which lipid metabolites accounted for the largest proportion. Correlation analysis showed that circulatory metabolites were significantly correlated with changes in airway microbiota composition. ConclusionsYH buccal tablets can inhibit opportunistic pathogens, increase beneficial microorganisms in the upper respiratory tract, and regulate the body's metabolic pathways. These findings provide insights into the mechanism of action of YH buccal tablets in the treatment and prevention of respiratory diseases.