Exploring the plausible genetic relationship of salivary and tongue microbiome with periodontitis: A mendelian randomization study.

Chronic periodontitis (CP) is associated with subgingival microbial dysbiosis and demonstrates specific microbial patterns, though definitive causal connections with microbiomes in distinct anatomical regions remain undetermined. Genome-wide association datasets for CP and oral microbial communities were sourced from a large European cohort and China National GeneBank DataBase (CNGBdb), respectively. Employing single-nucleotide polymorphisms (SNPs) as genetic instruments, Mendelian randomization (MR) analyses were conducted through the inverse-variance weighted (IVW) approach. Analysis methods were implemented through the 'TwoSampleMR' package (v0.6.4) in R software. Sensitivity analyses were performed to validate the robustness of the findings and mitigate the occurrence of horizontal pleiotropy. The MR analyses revealed three salivary bacterial taxa, Neisseria meningitidis (OR = 0.67, 95% CI, 0.49-0.98), Streptococcus vestibularis (OR = 0.74, 95% CI, 0.56-0.98), and Lancefieldella unclassified (OR = 0.68, 95% CI, 0.52-0.91) to be significantly associated with a reduced risk of CP (p < 0.05). In contrast, tongue microbial taxa Solobacterium unclassified (OR = 1.45, 95% CI, 1.04-2.04), Fusobacterium sp000235465 (OR = 1.40, 95% CI, 1.02-1.94), and Haemophilus parainfluenzae (OR = 1.56, 95% CI, 1.12-2.18) were associated with an increased CP risk (p < 0.05). No evidence of heterogeneity and directional pleiotropy was noted for these associations. This study highlights the association between specific salivary and tongue microbial taxa and CP, providing mechanistic linkages into the plausible relationship. It also suggests that some microbial taxa may be further explored as indicators for risk-stratified preventive measures and novel targets for precision prebiotics and therapies.