Circulating metabolites on dental caries risk: A Mendelian randomization study

Area of Science:

• Metabolomics
• Genetics
• Dental Public Health

Background:

• Observational studies have limitations in establishing causality for dental caries risk factors.
• Circulating serum metabolites represent systemic biochemical processes that may influence oral health.
• Understanding the causal links between metabolites and dental caries can inform prevention strategies.

Purpose of the Study:

• To investigate the causal effects of 1400 circulating serum metabolites on dental caries risk.
• To utilize a two-sample Mendelian randomization (MR) design for robust causal inference.
• To identify specific metabolites that could serve as biomarkers or therapeutic targets for dental caries.

Main Methods:

• A two-sample Mendelian randomization (MR) study was conducted.
• Genetic instruments for 1400 serum metabolites were derived from a genome-wide association study (GWAS) of 8299 individuals.
• Genetic association data for dental caries were obtained from the FinnGen consortium (N=500,348).
• Inverse-variance weighted (IVW) method was used for primary analysis, with MR-Egger and weighted median as sensitivity analyses.

Main Results:

• Twenty-four metabolites showed a significant causal effect on dental caries risk.
• Increased levels of 16 metabolites, including sphingomyelin variants and flavin adenine dinucleotide, were associated with higher caries risk.
• Reduced risk of dental caries was associated with lower levels of 8 metabolites, notably 5-methylthioadenosine and palmitoyl dihydrosphingomyelin.

Conclusions:

• Systemic metabolic and inflammatory processes may play a causal role in dental caries.
• Dental caries risk is potentially influenced by the host's underlying metabolic state, beyond traditional factors.
• Identified metabolites may serve as potential biomarkers for risk stratification and targets for novel preventive interventions.