Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral-gut and gut-oral axes through bidirectional Mendelian randomization

Abstract

Aim: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis.

Materials and methods: We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis.

Results: We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014.

Conclusions: The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.

Keywords: Mendelian randomization; gut microbiome; gut-oral axis; oral-gut axis; periodontitis.