Unraveling the Gut-Oral Axis: A Mendelian Randomization Analysis of Gut Microbiota Impact on Periodontitis via Circulating Inflammatory Proteins
British Journal of Hospital Medicine, 2025
Tang Y., Gao S., Wang Y., Liang W., Jin S., Weng Y., Xia Y., Ma J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Other Diseases & Syndromes | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Aims/Background Gut microbiota (GM) dysbiosis may exacerbate periodontitis by impairing intestinal barrier integrity and inducing systemic inflammation. However, the causal relationships and mediating roles of inflammatory proteins remain unclear. This study aimed to clarify these causal pathways and mediating mechanisms.
Methods Two-sample and multivariable Mendelian randomization (MR) analyses were conducted to evaluate the causal association between GM and periodontitis using publicly available genome-wide association study (GWAS) data and FinnGen repository. Causal estimates were obtained through inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode approaches. Additionally, MR-Egger regression and Cochran’s Q-test were applied to detect and correct for potential pleiotropy and heterogeneity.
Results Significant causal relationships were identified between GM genetics and periodontitis risk. Protective effects were observed for the class Actinobacteria (odds ratio [OR]: 0.726, 95% confidence interval [CI]: 0.574–0.918; p = 0.007), the genus Collinsella (OR: 0.655, 95% CI: 0.456–0.941; p = 0.022), the genus Ruminococcus 1 (OR: 0.692, 95% CI: 0.497–0.964; p = 0.029), the genus Sutterella (OR: 0.697, 95% CI: 0.541–0.897; p = 0.005), and the phylum Actinobacteria (OR: 0.712, 95% CI: 0.551–0.921; p = 0.010), whereas the genus Alistipes was identified as a risk factor (OR: 1.682, 95% CI: 1.240–2.280; p = 0.001). Furthermore, fractalkine potentially mediated 13.37% of the association between the phylum Actinobacteria and periodontitis. No evidence for reverse causation was found between periodontitis risk and the aforementioned six gut microbiota in the bidirectional MR analysis.
Conclusion Specific GM taxa and fractalkine exert causal effects on periodontitis, supporting the existence of a gut-oral axis mediated by systemic inflammation. These findings suggest potential therapeutic strategies targeting GM dysbiosis and inflammatory pathways.