# Causal links between gut microbiota, plasma metabolites, and insomnia: Insights from Mendelian randomization

## TL;DR

This study finds that gut microbiota may influence insomnia risk through specific plasma metabolites, offering new insights into gut-brain connections.

## Contribution

The study identifies causal links and mediation effects between gut microbiota, plasma metabolites, and insomnia using Mendelian randomization.

## Key findings

- Increased abundance of gut microbiome species like CAG-145 sp000435615 is linked to higher insomnia risk.
- The plasma metabolite 3-ethylcatechol sulphate mediates up to 31.49% of the effect of gut microbiota on insomnia.
- MR analysis identified 10 gut microbiomes and 35 plasma metabolites potentially associated with insomnia.

## Abstract

This study explored the plasma metabolites’ mediation effect between gut microbiomes and insomnia through Mendelian randomisation (MR).

Using publicly accessible GWAS data from 5959 individuals for gut microbiota and 8299 individuals for plasma metabolites, we employed MR analysis to explore their causal effects on insomnia. Insomnia outcome data were obtained from Pan-UKB, GERA, and FinnGen, covering 9007 cases and 871,802 controls. Mediation effects of identified bacterial taxa on insomnia through plasma metabolites were computed using the product of coefficients approach.

Our MR analysis included participants with a mean age of 45.7 years (SD = 11.5) for gut microbiota and 63 years (range 45–85) for plasma metabolites. The analysis identified 10 gut microbiomes and 35 plasma metabolites potentially associated with insomnia respectively. Specifically, increased abundances of certain gut microbiomes, such as species CAG-145 sp000435615, were linked to a higher risk of insomnia. Mediation analysis revealed that the plasma metabolite 3-ethylcatechol sulphate levels significantly mediated the effects of these microbiomes on insomnia, explaining up to 31.49% of the total effect.

This study highlights the role of gut microbiota in influencing insomnia risk, mediated through specific plasma metabolites. These findings provide valuable insights into the gut-brain axis and may inform the development of therapeutic targets for managing sleep disorders.