Gut Microbiota, Immune Phenotypes, and Insomnia: A Two-Sample Mendelian Randomization Study.

IF 3.4 2区医学 Q2 CLINICAL NEUROLOGY

Nature and Science of Sleep Pub Date : 2026-06-24 eCollection Date: 2026-01-01 DOI:10.2147/NSS.S597195

Xiaofeng Jiang, Bin Yu

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引用次数: 0

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 Blautia genus at the species level, where Blautia A sp900066355 showed a robust protective association (surviving FDR correction), whereas other species within the genus increased risk at a nominal significance level (uncorrected P < 0.05). Furthermore, 17 immune phenotypes were found to be associated with insomnia. Exploratory mediation analysis suggested that monocytic myeloid-derived suppressor cells (M-MDSCs) may mediate the pathway linking the uncultured bacterium CAG-177 to insomnia, accounting for 10.7% of the total effect.

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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肠道菌群、免疫表型和失眠：一项双样本孟德尔随机研究。

目的：微生物-肠-脑轴为理解失眠提供了一个新的框架；然而，特异性免疫途径介导肠道微生物群对失眠的因果影响的假设需要支持遗传证据。本研究旨在利用大规模遗传数据，探索支持肠道微生物群、免疫表型和失眠之间因果相互作用的遗传证据。患者和方法：我们采用双样本双向孟德尔随机化（MR），使用大规模全基因组关联研究（GWAS）汇总统计肠道微生物群、731种免疫细胞表型和失眠（FinnGen R12）。进行中介分析以量化免疫细胞的特异性间接效应。结果：我们发现了13个肠道微生物类群与失眠风险有关的启发性遗传证据。值得注意的是，在物种水平上，在Blautia属内观察到方向性差异，其中Blautia a sp900066355显示出强大的保护关联（幸存的FDR校正），而属内的其他物种在名义显著水平上增加了风险（未校正P < 0.05）。此外，17种免疫表型被发现与失眠有关。探索性中介分析表明，单核细胞髓源性抑制细胞（M-MDSCs）可能介导未培养细菌CAG-177与失眠之间的通路，占总效应的10.7%。结论：本研究提供了将特定肠道微生物分类群和免疫表型与失眠风险联系起来的初步遗传证据，Blautia A sp900066355显示出强大的保护作用。作为次要假设，我们提出了一个初步假设，即保护性M-MDSCs的消耗，而不仅仅是促炎激活，可能导致失眠的发病机制。鉴于这一中介发现的临界统计意义，目前得出直接的治疗意义还为时过早。

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来源期刊

Nature and Science of Sleep Neuroscience-Behavioral Neuroscience

CiteScore

5.70

自引率

5.90%

发文量

245

审稿时长

16 weeks

期刊介绍： Nature and Science of Sleep is an international, peer-reviewed, open access journal covering all aspects of sleep science and sleep medicine, including the neurophysiology and functions of sleep, the genetics of sleep, sleep and society, biological rhythms, dreaming, sleep disorders and therapy, and strategies to optimize healthy sleep. Specific topics covered in the journal include: The functions of sleep in humans and other animals Physiological and neurophysiological changes with sleep The genetics of sleep and sleep differences The neurotransmitters, receptors and pathways involved in controlling both sleep and wakefulness Behavioral and pharmacological interventions aimed at improving sleep, and improving wakefulness Sleep changes with development and with age Sleep and reproduction (e.g., changes across the menstrual cycle, with pregnancy and menopause) The science and nature of dreams Sleep disorders Impact of sleep and sleep disorders on health, daytime function and quality of life Sleep problems secondary to clinical disorders Interaction of society with sleep (e.g., consequences of shift work, occupational health, public health) The microbiome and sleep Chronotherapy Impact of circadian rhythms on sleep, physiology, cognition and health Mechanisms controlling circadian rhythms, centrally and peripherally Impact of circadian rhythm disruptions (including night shift work, jet lag and social jet lag) on sleep, physiology, cognition and health Behavioral and pharmacological interventions aimed at reducing adverse effects of circadian-related sleep disruption Assessment of technologies and biomarkers for measuring sleep and/or circadian rhythms Epigenetic markers of sleep or circadian disruption.