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

XuWen Zheng1, Jin Xu1, JinNan Yin1

  • 1Department of Emergency, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.

Dialogues in Clinical Neuroscience
|February 27, 2026
PubMed
Abstract

Insights

Gut bacteria influence insomnia risk through plasma metabolites. Specific gut microbiomes and 3-ethylcatechol sulphate levels mediate this connection, offering potential therapeutic targets for sleep disorders.

Area of Science:

  • Microbiome research
  • Metabolomics
  • Sleep science

Background:

  • The gut microbiome plays a role in the gut-brain axis.
  • Understanding the link between gut microbiota and insomnia is crucial for public health.
  • Plasma metabolites may mediate the effects of gut bacteria on sleep.

Purpose of the Study:

  • To investigate the mediating role of plasma metabolites in the relationship between gut microbiomes and insomnia.
  • To identify specific gut bacteria and plasma metabolites associated with insomnia.
  • To explore potential therapeutic targets for insomnia based on gut-brain axis interactions.

Main Methods:

  • Mendelian randomization (MR) analysis was used to explore causal relationships.
  • Genome-wide association study (GWAS) data for gut microbiota and plasma metabolites were utilized.
  • Mediation effects were calculated using the product of coefficients approach.

Main Results:

  • Ten gut microbiomes and 35 plasma metabolites were found to be potentially associated with insomnia.
  • Increased abundance of certain gut microbiomes, like CAG-145 sp000435615, correlated with higher insomnia risk.
  • Plasma metabolite 3-ethylcatechol sulphate significantly mediated the effect of gut microbiomes on insomnia, explaining up to 31.49% of the total effect.

Conclusions:

  • Gut microbiota composition influences insomnia risk.
  • Plasma metabolites, such as 3-ethylcatechol sulphate, act as mediators in the gut-brain axis concerning insomnia.
  • These findings suggest novel therapeutic strategies for managing insomnia by targeting the gut microbiome and its metabolites.
Keywords:
Gut microbiotaMendelian randomisationinsomnia

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