Causal effects of gut microbiota on the risk of periodontitis: a two-sample Mendelian randomization study

Abstract

IntroductionThe oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis.MethodsSNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.ResultsNine gut microbiota taxa (Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales, Pasteurellales, Enterobacteriaceae, Pasteurellaceae, Bacteroidales S24.7 group, Alistipes, and Eisenbergiella) are predicted to play a causal role in enhancing the risk of periodontitis (p< 0.05). Besides, two gut microbiota taxa (Butyricicoccus and Ruminiclostridium 6) have potentially inhibitive causal effects on the risk of periodontitis (p< 0.05). No significant estimation of heterogeneity or pleiotropy is detected.ConclusionOur study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.

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

“…Utilizing whole-genome sequencing and bioinformatics analysis, the study identified that Bacteroidia, encompassing the order Bacteroidales, demonstrated notable diversity and abundance in the oral cavity ( Caselli et al., 2020 ). Based on preceding investigations, it was noted that Bacteroidales represented one of the taxa exhibiting a marked adverse effect on gingivitis ( Luo et al., 2023 ). However, conflicting outcomes emerge from an observational study, suggesting the anti-inflammatory properties of metabolites originating from the Bacteroidales group ( Luo et al., 2023 ).…”

“…Based on preceding investigations, it was noted that Bacteroidales represented one of the taxa exhibiting a marked adverse effect on gingivitis ( Luo et al., 2023 ). However, conflicting outcomes emerge from an observational study, suggesting the anti-inflammatory properties of metabolites originating from the Bacteroidales group ( Luo et al., 2023 ). Indeed, our MR study can overcome these challenges by providing validation from a genetic perspective, presenting clear evidence that the class Bacteroidia group contribute to the risk of gingivitis.…”

“…For example, experimental research has highlighted the role of Bacteroides in exacerbating gingivitis ( Caselli et al., 2020 ). However, this stands in contrast to observational studies that propose the anti-inflammatory effects of Bacteroides metabolites, presenting a complex narrative ( Luo et al., 2023 ). To navigate these complexities, MR offers a unique approach.…”

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

“…Luo et al (2023) examined the causal effect of GM taxa on periodontitis and identified 10 GM taxa that may potentially have causal effects on periodontitis. However, their research did not investigate the causal effects of periodontitis on GM taxa.…”

“…Owing to the random nature of meiosis, MR analyses are not subject to reverse causation or confounding. A recent MR study has reported that certain GM taxa may exert causal effects on periodontitis (Luo et al, 2023). However, the causal effects of periodontitis on GM taxa were not elucidated.…”