ArticleNature and science of sleep2026
Gut Microbiota, Immune Phenotypes, and Insomnia: A Two-Sample Mendelian Randomization Study.
Article in Nature and science of sleep, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: The microbiota-gut-brain axis offers a novel framework for understanding insomnia; however, the hypothesis that specific immune pathways mediate the causal effects of gut microbial taxa on insomnia requires supporting genetic evidence. This study aimed to explore the genetic evidence supporting the causal interplay between the gut microbiota, immune phenotypes, and insomnia using large-scale genetic data. Patients and Methods: We employed two-sample bidirectional Mendelian Randomization (MR) using large-scale genome-wide association study (GWAS) summary statistics for gut microbiota, 731 immune cell phenotypes, and insomnia (FinnGen R12). Mediation analysis was conducted to quantify the specific indirect effects of immune cells. Results: We found suggestive genetic evidence linking 13 gut microbial taxa to insomnia risk. Notably, a directional divergence was observed within the Conclusion: This study provides preliminary genetic evidence linking specific gut microbial taxa and immune phenotypes to insomnia risk, with Blautia A sp900066355 demonstrating robust protective effects. As a secondary hypothesis-generating observation, we propose a preliminary hypothesis that the depletion of protective M-MDSCs, rather than solely pro-inflammatory activation, may contribute to insomnia pathogenesis. Given the borderline statistical significance of this mediation finding, drawing direct therapeutic implications is currently premature.
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