Occlusal types shape oral microbiome stomatotypes and metabolic landscapes: A multi-omics perspective on host-microbe interaction.

Clinical studies have uncovered associations between malocclusions and bacteria-related oral diseases. However, which malocclusion drives alternations in the oral microbiome remains unclear. Here, we identified occlusal type (OT, a major malocclusion classification parameter) as a key host structural regulator of the oral microbiome composition and metabolite profiles in adolescents. Regarding microbial composition: Prevotella and Veillonella species enriched in the OT-I group, whereas Neisseria and Haemophilus species predominated in the OT-II group. These differential distributions and unique microbial associations contributed to the formation of two distinct oral microbiome clusters ("stomatotypes"). In terms of gene functions, the OT-II group exhibited enrichment in "Environmental information processing" (EIP) pathways, "Human Diseases" (HD) pathways, and virulence-associated genes including relA and cpsB/cdsA. Significant differences in metabolite profiles were also observed between groups. Multi-omics analysis revealed positive intra-group associations and negative associations between-groups among representative oral microbes, functional pathways, and metabolites, with specific dipeptides identified as potential key microbe-modulated metabolites. Our results revealed the pivotal role of OT in shaping the variations of the oral microbiome and metabolite, offering novel insights into how host anatomical structure influences oral microecology.