Oral Microbiome and Constipation: A Causal Link Revealed by Mendelian Randomization

ABSTRACT Background Constipation affects approximately 15.3% of the global population. While the gut microbiome's role in constipation has been studied, the causal relationship between the oral microbiome and constipation remains unexplored. Methods We utilized Mendelian randomization (MR) and large‐scale GWAS data to investigate the causal relationship between the oral microbiome and constipation. Oral microbiome data were sourced from a metagenome‐wide association study (mgGWAS) on 2984 individuals, while constipation GWAS data came from 176 629 samples in the Japan Biobank. Statistical methods included inverse variance‐weighted (IVW) analysis, weighted median, and MR‐Egger regression. Results The MR analysis revealed significant associations between specific oral microbiome and constipation. Treponema denticola , found in saliva, was positively associated with an increased risk of constipation (OR = 3.961, 95% CI = 1.085–14.453, p = 0.037). Conversely, certain bacteria like Pauljensenia sp000308055 showed protective effects (OR = 0.409, 95% CI = 0.167–0.999, p = 0.0496). In the tongue coating, Neisseria sicca exhibited a significant positive association with constipation (OR = 4.864, 95% CI = 1.293–18.302, p = 0.019), while Aggregatibacter segnis demonstrated a protective effect (OR = 0.400, 95% CI = 0.188–0.854, p = 0.018). Conclusion This study is the first to explore the potential causal relationship between oral microbiome and constipation. The findings suggest that specific oral bacteria may influence the risk of constipation, highlighting the need for further research to validate these relationships and understand the mechanisms involved. Moreover, the study underscores the importance of considering both oral and gut microbiome in the context of gastrointestinal health and disease management.