Integrated Oral Microbiome Profiling from Aligners, Saliva, and Plaque Identifies Biosynthetic Signatures of Disease

The oral cavity harbours a complex microbial ecosystem and a key interface with the external environment. To gain a broader and more temporally resolved understanding of the oral microbiome, we analysed 1,242 samples from 585 individuals, including specimens from aligners, plaque, and saliva across healthy individuals and patients with caries or periodontitis. We found that clear aligners, worn continuously, provide a notably stable and comprehensive snapshot of oral microbial diversity, capturing 399 species and substantially overlapping with saliva. While only 25 species showed disease-associated differences, functional profiling revealed an extensive biosynthetic capacity, with 41,923 biosynthetic gene clusters organized into 1,786 families. Among these, 103 gene cluster families showed differential abundance in disease states and included both characterized antimicrobials and potentially novel metabolites. This study underscores the value of functional microbiome profiling in advancing precision oral health.