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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Neuroinflammation and Neuropathy
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1400426

Interplay between Immune Cells and Metabolites in Epilepsy: Insights from a Mendelian Randomization Analysis

Provisionally accepted
Kai Wang Kai Wang Yu Wang Yu Wang *Jinwei Yang Jinwei Yang Wenhao Xu Wenhao Xu Lei Wang Lei Wang
  • Department of Neurology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, China

The final, formatted version of the article will be published soon.

    Background: Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy.We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results.Results: MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI: -0.008%, -30.6%, P=0.049) of the effect of DN (CD4-CD8-) AC on epilepsy. 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI: 0.668%, 10.6%, P=0.026) and X-12544 levels (95%CI: -15.1%, -0.856%, P=0.028) contributed 5.63% and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy.This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives.

    Keywords: Epilepsy, immune cells, Metabolites, Causal relationships, Mendelian randomization

    Received: 04 Apr 2024; Accepted: 17 Jul 2024.

    Copyright: © 2024 Wang, Wang, Yang, Xu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yu Wang, Department of Neurology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.