Investigating bidirectional causal relationships between gut microbiota and insomnia

Shangyun Shi; Dongming Liu; Ancha Baranova; Hongbao Cao; Fuquan Zhang

doi:10.1136/gpsych-2024-101855

Investigating bidirectional causal relationships between gut microbiota and insomnia

Gen Psychiatr. 2025 Aug 12;38(4):e101855. doi: 10.1136/gpsych-2024-101855. eCollection 2025.

Authors

Shangyun Shi¹, Dongming Liu², Ancha Baranova^{3

4}, Hongbao Cao³, Fuquan Zhang^{1

5}

Affiliations

¹ Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
² Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
³ School of Systems Biology, George Mason University, Fairfax, Virginia, USA.
⁴ Research Center for Medical Genetics, Moscow, Russia.
⁵ Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

Background: Although studies in recent years have explored the impact of gut microbiota on various sleep characteristics, the interaction between gut microbiota and insomnia remains unclear.

Aims: We aimed to evaluate the mutual influences between gut microbiota and insomnia.

Methods: We conducted Mendelian randomisation (MR) analysis using genome-wide association studies datasets on insomnia (N=386 533), gut microbiota data from the MiBioGen alliance (N=18 340) and the Dutch Microbiome Project (N=8208). The inverse variance weighted (IVW) technique was selected as the primary approach. Then, Cochrane's Q, Mendelian randomization-Egger (MR-Egger) and MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) tests were used to detect heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of the MR results. In addition, we performed the Steiger test to thoroughly verify the causation.

Results: According to IVW, our results showed that 14 gut bacterial taxa may contribute to the risks of insomnia (odds ratio (OR): 1.01 to 1.04), while 8 gut bacterial taxa displayed a protective effect on this condition (OR: 0.97 to 0.99). Conversely, reverse MR analysis showed that insomnia may causally decrease the abundance of 7 taxa (OR: 0.21 to 0.57) and increase the abundance of 12 taxa (OR: 1.65 to 4.43). Notably, the genus Odoribacter showed a significant positive causal relationship after conducting the Steiger test. Cochrane's Q test indicated no significant heterogeneity between most single-nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to MR-Egger and MR-PRESSO.

Conclusions: Our study highlighted the reciprocal relationships between gut microbiota and insomnia, which may provide new insights into the treatment and prevention of insomnia.

Keywords: Causality; Mendelian Randomization Analysis.