Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures. Currently, the associations among skin microbiota, circulating metabolites, and epilepsy are still not well studied. In this study, we applied univariate and two-step Mendelian randomization analysis using single nucleotide polymorphisms as instrumental variables to analyze the possible associations. Five skin microbiota (asv022, asv008, bacillales, clostridiale, and micrococcaceae) and four circulating metabolites were found to be associated with epilepsy. Our results also showed that leucine level (p-value = 0.0487, OR = 1.067) and glutamine level (p-value = 0.0372, OR = 1.065) show a slight increased association with epilepsy, while phospholipids in medium LDL (p-value = 0.0302, OR = 0.9308) and ratio of saturated fatty acids (p-value = 0.0309, OR = 0.9017) appear to show a slight inverse correlation with epilepsy. In addition, the heterogeneity test and horizontal pleiotropy analysis indicated these results are robust in different situations. By mapping analysis, 54 genes were associated with at least two metabolites. By functional analysis, these genes were enriched in the immune-related pathways, which may have systemic effects on brain function. Our results provide a novel insight for understanding possible mechanisms of some epilepsy associations, which by further study might provide avenues for therapy research.
Keywords: Mendelian randomization analysis; circulating metabolic biomarker; epilepsy; skin microbiota.