Investigating bidirectional causal relationships between gut microbiota and insomnia

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.

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

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.

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.

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