Causal relationship between the gut microbiota and insomnia: a two-sample Mendelian randomization study

Abstract

Background: Changes in the gut microbiota are closely related to insomnia, but the causal relationship between them is not yet clear.

Objective: To clarify the relationship between the gut microbiota and insomnia and provide genetic evidence for them, we conducted a two-sample Mendelian randomization study.

Methods: We used a Mendelian randomized two-way validation method to discuss the causal relationship. First, we downloaded the data of 462,341 participants relating to insomnia, and the data of 18,340 participants relating to the gut microbiota from a genome-wide association study (GWAS). Then, we used two regression models, inverse-variance weighted (IVW) and MR-Egger regression, to evaluate the relationship between exposure factors and outcomes. Finally, we took a reverse MR analysis to assess the possibility of reverse causality.

Results: The combined results show 19 gut microbiotas to have a causal relationship with insomnia (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.01, 1.05; p=0.000 for class. Negativicutes; OR: 1.03; 95% CI: 1.01, 1.05; p=0.000 for order.Selenomonadales; OR: 1.01; 95% CI: 1.00, 1.02; p=0.003 for genus.RikenellaceaeRC9gutgroup). The results were consistent with sensitivity analyses for these bacterial traits. In reverse MR analysis, we found no statistical difference between insomnia and these gut microbiotas.

Conclusion: This study can provide a new direction for the causal relationship between the gut microbiota (class.Negativicutes, order.Selenomonadales, genus.Lactococcus) and insomnia and the treatment or prevention strategies of insomnia.

Keywords: Mendelian randomization; bacterial traits; causal relationship; gut microbiota; insomnia.