Multi-Omics Insights into Gingivitis from a Clinical Trial: Understanding the Role of Bacterial and Host Factors

Poor oral health is a neglected epidemic, potentially contributing to systemic health issues. We employed a multi-omics approach to investigate the biological changes associated with gingivitis and the effects of stannous fluoride (SnF₂) dentifrice on microbial composition and salivary proteomics in an eight-week clinical trial involving 39 participants categorized as high (<i>n</i> = 20) and low bleeders (<i>n</i> = 19). Baseline assessments revealed significant microbial dysbiosis in high bleeders, characterized by a higher abundance of <i>Porphyromonas</i> and <i>Fusobacterium</i>, alongside compromised epithelial barriers and increased inflammation. Following SnF₂ treatment, a substantial reduction in these bacteria, and an increase in <i>Rothia</i> and <i>Haemophulis</i>, were observed, correlating with improved clinical measures, including reduced bleeding and inflammation indices. In total, 80 proteins (including pro-inflammatory cytokines, alarmin keratins, and matrix metalloproteinases) showed a significant reduction in high bleeders after treatment, with 29 overlapping the disease biomarkers in the plasma atlas, supporting the role of SnF₂ in mitigating oxidative stress and enhancing epithelial integrity. Furthermore, SnF₂ treatment significantly reduced collagen degradation, suggesting the preservation of tissue integrity. These findings highlight that SnF₂ not only improves local oral health but may also benefit systemic health, showcasing the value of a multi-omics approach in understanding the interconnections among oral microbiota, inflammatory responses, and systemic health outcomes.