Assessing links between dental fluorosis and oral/systemic health via salivary microbiome in Chinese young adults

Objectives: This study utilized dual control groups, caries patients (a representative bacterial infectious disease) and healthy individuals, to identify the core microbiome specific to dental fluorosis and elucidate the potential associations with systemic health and diseases from the perspective of the oral–gut–lung axis. Methods: Initially, 1001 volunteers were recruited, among whom 959 provided complete questionnaire data. In subsequent omics analyses, saliva samples from 387 participants (HC: n = 117; DC: n = 138; DF: n = 132) were included, and background confounders were controlled via partial correlation analysis. Multidimensional analyses based on 16S rRNA sequencing revealed significant intergroup separation of microbial communities. Results: By comparing differentially abundant taxa across pairwise comparisons (HC vs DC, HC vs DF, DC vs DF), 24 key DF-associated microorganisms were identified. These microbial markers exhibited high diagnostic accuracy, with area under the receiver operating characteristic curve values of 92.6% and 89.3% for distinguishing DF from HC and DF from DC, respectively. t-SNE dimensionality reduction further confirmed that the microbial signature clearly separated the DF group from both HC and DC groups. Microbial co-occurrence network analysis revealed significant positive correlations between Enhydrobacter and Caulobacter, Mycobacterium and Enhydrobacter, and Mycobacterium and Caulobacter. Conclusions: This study provides evidence at the transmissible microecological level that dental fluorosis possesses a distinct microbiome profile compared to dental caries. In addition, the long-term periodontal status of patients with dental fluorosis and its potential link to periodontitis, intestinal and respiratory system diseases merit further investigation.