Investigating the causal relationship between human blood/urine metabolites and periodontal disease using two-sample Mendelian randomization

Background and Aims: The aim is to investigate the cause-and-effect connection between metabolites found in blood/urine and the likelihood of developing periodontal disease (PD) through the utilization of a two-sample Mendelian randomization (MR) method. Methods: Using an inverse variance weighted (IVW) method and two additional two-sample MR models, we examined the relationship between blood/urine metabolites and PD by analyzing data from a comprehensive metabolome-based genome-wide association study and the Genome-Wide Association Studies (GWAS) of PD. To assess the consistency and dependability of the findings, diversity, cross-effects, and sensitivity analyses were conducted. Results: Out of the 35 metabolites found in blood and urine, a total of eight metabolites (C-reactive protein, Potassium in urine, Urea, Cystatin C, Non-albumin protein, Creatinine, estimated Glomerular Filtration Rate, and Phosphate) displayed a possible causal connection with the risk of dental caries/PD using the inverse variance weighted (IVW) method (p < 0.05). This includes five metabolites in the blood and three in the urine. No metabolites were statistically significant in IVW MR models (p < 3.68 x 10(-4)). Even after conducting sensitivity analysis with the leave-one-out method and removing the confounding instrumental variables, the impact of these factors on dental caries/PD remained significant. Conclusion: Based on the available evidence, it is not possible to establish a significant causal link between the 35 blood metabolites and the likelihood of developing dental caries and PD.