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

Abstract

BackgroundChanges in the gut microbiota are closely related to insomnia, but the causal relationship between them is not yet clear.ObjectiveTo clarify the relationship between the gut microbiota and insomnia and provide genetic evidence for them, we conducted a two-sample Mendelian randomization study.MethodsWe 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.ResultsThe 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.ConclusionThis 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.

Traditional Chinese herbal formulas modulate gut microbiome and improve insomnia in patients with distinct syndrome types: insights from an interventional clinical study

“…Notably, a previous study found that depletion of the gut microbiota by antibiotics significantly affects sleep/wake behavior, potentially through disruptions in neurotransmitter balances, such as serotonin, underscoring the microbiome’s regulatory capacity on sleep ( Ogawa et al., 2020 ). Additionally, a more recent study proposes a causal link between specific gut microbiotas and insomnia via a Mendelian randomized two-way validation method ( Wang et al., 2024 ). These findings highlight the complexity of the gut-brain axis and its implications for sleep disorders.…”