Longitudinal multi-omics along gingivitis development reveal a suboptimal-health gum state with periodontitis-like microbiome

Most adults experience episodes of gingivitis, which can progress to the irreversible, chronic state of periodontitis. However the mechanistic roles of plaque in gingivitis onset and progression to periodontitis remain elusive. Here, we integrated the longitudinal multi-omics data from plaque metagenome, metabolome and salivary cytokines in 40 adults who transit from naturally-occurring gingivitis (NG), to healthy gingivae (baseline) and then to experimental gingivitis (EG). During EG, rapid and consistent alterations in plaque microbiota, metabolites and salivary cytokines emerged as early as 24-72 hours after pause of oral hygiene, defining an asymptomatic ‘sub-optimal health’ (SoH) stage. SoH also features a steep and synergetic decrease of plaque-derived betaine and Rothia spp., suggesting an anti-gum-inflammation mechanism by health-promoting microbial residents. Global, cross-cohort meta-analysis revealed a high Microbiome-based Periodontitis Index at SoH state, due to its convergent taxonomical and functional profiles towards those of periodontitis. In contrast, caries SoH features a microbial signature very distinct from caries. Thus SoH is a universal state of polymicrobial inflammations with disease-specific features, which is key to maintaining a disease-preventive plaque. ### Competing Interest Statement The authors have declared no competing interest.