Anatomizing causal relationships between gut microbiota, plasma metabolites, and epilepsy: A mendelian randomization...

Area of Science:

• Neuroscience
• Microbiology
• Metabolomics

Background:

• Epilepsy imposes a significant disease burden.
• Gut microbiota (GM) influences epilepsy progression.
• Plasma metabolites may mediate the GM-epilepsy connection, but causal links are under-investigated.

Purpose of the Study:

• To investigate the causal relationships between GM, plasma metabolites, and epilepsy.
• To identify potential metabolite mediators in the GM-epilepsy axis.

Main Methods:

• Utilized Mendelian randomization (MR) analysis.
• Employed large-scale genome-wide meta-analyses for GM, plasma metabolites, and epilepsy in European ancestry.
• Applied two-step MR (TSMR) to identify mediating metabolites.

Main Results:

• Identified 19 gut microbial taxa causally associated with epilepsy risk, with Omnitrophota phylum showing the strongest association.
• Found 21 plasma metabolites linked to epilepsy, notably eastotal fatty acids.
• Observed an indirect effect of the free cholesterol to total lipids ratio in large LDL, mediating the association between Fournierella massiliensis and epilepsy.

Conclusions:

• Established a causal link between Fournierella massiliensis, the free cholesterol to total lipids ratio in large LDL, and epilepsy.
• Confirmed the mediating role of the free cholesterol to total lipids ratio in large LDL in epilepsy.