Comprehensive Analysis of Orthodontic Treatment Effects on the Oral Microbiome, Metabolome, and Associated Health Indicators.

INTRODUCTION AND AIMS: Effects of orthodontic treatments on oral health, particularly on the microbiome and metabolome, are not well understood, and this study aims to clarify these influences using multi-omics approaches. METHODS: We used 16SrRNA sequencing to analyze oral microbiota and untargeted metabolomics for metabolic profiling, comparing clear aligners (CAs) and fixed appliances (FAs) in healthy and unhealthy oral environments. RESULTS: We found CAs significantly improve oral health markers-including reduced plaque accumulation, enamel demineralization, microbiome alpha diversity, and microbial heterogeneity, especially in unhealthy oral environments. Orthodontic treatment type and overall oral health status significantly altered the oral microbiota structure and metabolite composition. Notably, the effect of orthodontic methods was more pronounced on metabolome than on microbiome. There's a strong link between changes in oral microbiome, health status, and hygiene habits. For example, Prevotella and Treponema were linked to poor oral health indicators, whereas Rothia, Granulicatella, and Streptococcus were associated with good oral hygiene indicators. Machine learning analysis identified 13 key metabolites, including cholylarginine, alpha-CEHC glucuronide, 2-hydroxypentanoic acid, Cer (d17:1/6 keto-PGF1alpha), and LysoPE (15:0/0:0), which were associated with inflammatory responses and served as predictive markers for poor oral health. These metabolites were closely correlated with specific microbial species enriched in oral environment, including Rothia, Prevotella, and Anaeroglobus, suggesting their potential as biomarkers for oral health monitoring. KEGG enrichment revealed differential metabolites were significantly enriched in alkaloid biosynthesis pathways, particularly map01064, which is crucial for polyamine synthesis related to bacterial activities. CONCLUSION: CAs significantly improve oral health markers, particularly affecting the metabolome more than the microbiome, with key metabolites and microbial species serving as potential biomarkers for oral health monitoring. CLINICAL RELEVANCE: This study provides comprehensive insights into interactions among orthodontic treatments, oral health status, microbial, and metabolic dynamics, offering foundation for developing personalized strategies in oral health management and orthodontic care.