Genetic evidence strengthens the connection between gut microbiota and gingivitis: a two-sample Mendelian randomization study

遗传证据强化了肠道菌群与牙龈炎之间的联系:一项双样本孟德尔随机化研究

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Abstract

INTRODUCTION: The oral cavity and gut tract, being interconnected and rich in microbiota, may have a shared influence on gingivitis. However, the specific role of distinct gut microbiota taxa in gingivitis remains unexplored. Utilizing Mendelian Randomization (MR) as an ideal method for causal inference avoiding reverse causality and potential confounding factors, we conducted a comprehensive two-sample MR study to uncover the potential genetic causal impact of gut microbiota on gingivitis. METHODS: Instrumental variables were chosen from single nucleotide polymorphisms (SNPs) strongly associated with 418 gut microbiota taxa, involving 14,306 individuals. Gingivitis, with 4,120 cases and 195,395 controls, served as the outcome. Causal effects were assessed using random-effect inverse variance-weighted, weighted median, and MR-Egger methods. For replication and meta-analysis, gingivitis data from IEU OpenGWAS were employed. Sensitivity analyses included Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. This study aimed to assess the genetic correlation between the genetically predicted gut microbiota and gingivitis using linkage disequilibrium score regression (LDSC). RESULTS: Three gut microbiota taxa (class Actinobacteria id.419, family Defluviitaleaceae id.1924, genus Defluviitaleaceae UCG011 id.11287) are predicted to causally contribute to an increased risk of gingivitis (P< 0.05). Additionally, four gut microbiota taxa (class Actinobacteria id.419, genus Escherichia Shigella id.3504, genus Ruminococcaceae UCG002 id.11360) potentially exhibit inhibitory causal effects on the risk of gingivitis (P< 0.05). No significant evidence of heterogeneity or pleiotropy is detected. Our findings indicate a suggestive genetic correlation between class Actinobacteria id.419, class Bacteroidia id.912, family Defluviitaleaceae id.1924, genus Escherichia Shigella id.3504 and gingivitis. CONCLUSION: Our study establishes the genetic causal effect of 418 gut microbiota taxa on gingivitis, offering insights for clinical interventions targeting gingivitis. Subsequent research endeavors are essential to corroborate the findings of our present study.

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