Appraising the Effects of Gut Microbiota on Insomnia Risk Through Genetic Causal Analysis

Peihong Li; Song Wang; Jiaxin Li; Zheng Xiao; Haoyue Zhu; Dandan Sheng; Weiping Liu; Bo Xiao; Luo Zhou

doi:10.1002/ajmg.b.33021

Appraising the Effects of Gut Microbiota on Insomnia Risk Through Genetic Causal Analysis

Am J Med Genet B Neuropsychiatr Genet. 2025 Jan 3:e33021. doi: 10.1002/ajmg.b.33021. Online ahead of print.

Authors

Peihong Li^{1

2

3}, Song Wang⁴, Jiaxin Li^{1

2}, Zheng Xiao⁵, Haoyue Zhu^{1

2}, Dandan Sheng^{1

2

6}, Weiping Liu^{1

2}, Bo Xiao^{1

2}, Luo Zhou^{1

2}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
⁴ Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Department of Pathology, First Hospital of Changsha, Changsha, Hunan, China.
⁶ Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

PMID: 39754389
DOI: 10.1002/ajmg.b.33021

Abstract

BackgroundInsomnia is a common neurological disorder that exhibits connections with the gut microbiota; however, the exact causal relationship remains unclear. MethodsWe conducted a Mendelian randomization (MR) study to systematically evaluate the causal effects of genus-level gut microbiota on insomnia risk in individuals of European ancestry. Summary-level datasets on gut microbiota were sourced from the genome-wide association study (GWAS) of MiBioGen, while datasets on insomnia were obtained from the GWAS of Neale Lab and FinnGen. The primary analytical approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, maximum likelihood, MR-robust adjusted profile score, and weighted median. Sensitivity analyses were conducted to ensure robustness. ResultsThe microbial taxa Enterorhabdus, Family XIII AD3011 group, Paraprevotella, and Lachnospiraceae UCG004 were associated with an increased risk of insomnia, whereas Coprococcus1, Coprobacter, Desulfovibrio, Flavonifractor, Olsenella, Odoribacter, and Oscillibacter were linked to a decreased risk. Regarding the insomnia phenotype characterized by trouble falling asleep, the microbial taxon Eisenbergiella was correlated with an increased risk, while Haemophilus and the Eubacterium brachy group were associated with a reduced risk. Furthermore, for the insomnia phenotype characterized by waking too early, the microbial taxa Family XIII UCG001, Lachnospiraceae FCS020 group, and Olsenella were linked to an increased risk, whereas the Eubacterium brachy group and Victivallis were associated with a lower risk. The results remained robust across all sensitivity analyses. ConclusionOur MR study identified multiple genus-level gut microbial taxa that may exhibit potential causal effects on insomnia from a genetic perspective. These findings provide evidence supporting the theory of the microbiota-gut-brain axis and offer new insights into potential prevention and therapeutic targets for insomnia.

Keywords: Mendelian randomization; causal effects; gut microbiota; insomnia; microbiota‐gut‐brain axis.

Abstract

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