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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Preventive effects of compound probiotics supplementation on migraine: Mendelian randomization analysis and experimental evidence

  • Lu Bai1
  • Qingteng Zhang1,2
  • Jingyuan Zhu3
  • Wenqiang Zhang4
  • Zhenwu Cui5
  • Tian Jia1
  • Chaokun Li5
  • Zhiyue Guo5
5 affiliations
  1. 1Henan Medical University
  2. 2Department of Pathology, The Fifth Affiliated Hospital of Anhui Medical University
  3. 3The Third Clinical College, Henan Medical University
  4. 4The First Affiliated Hospital of Zhengzhou University
  5. 5Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Henan Medical University
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Abstract

Introduction: Migraine imposes a substantial economic and societal burden. The microbiota-gut-brain axis (MGBA) has emerged as a key potential mechanism, yet its causal relationships with migraine and the underlying pathways remain unclear.

Methods: We performed Mendelian randomization (MR) to assess the causal effects of gut microbiota on migraine, and further conducted mediation analysis to identify key mediating brain regions. In addition, we performed in vivo mouse experiments, in which we induced migraine-like pain via nitroglycerin (NTG) and investigated changes in gut microbiota, mechanical pain threshold, and regional brain activation following pretreatment with composite probiotics.

Results: MR analysis identified eight gut microbial taxa causally associated with migraine and its subtypes. Mediation analysis suggested that the association between genetically predicted Paraprevotella abundance and migraine risk was partially mediated by ICVF in the posterior insular cortex. In NTG-induced migraine mice, composite probiotics ameliorated gut dysbiosis and maintained Paraprevotella abundance, while elevating mechanical pain thresholds in both periorbital and hind paw region. Probiotics intervention also suppressed c-Fos expression in the pIC, Sp5c, PVT, and mPFC. Additionally, it specifically decreased CGRP immunoreactivity in the Sp5c.

Conclusion: This study provides genetic and experimental evidence supporting a potential role of the gut microbiome in migraine and the potential of microbiome-based strategies for migraine prevention.

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Cite

BibTeXRIS
BibTeX
@article{bai2026preventive,
  title = {{Preventive effects of compound probiotics supplementation on migraine: Mendelian randomization analysis and experimental evidence}},
  author = {Lu Bai and Qingteng Zhang and Jingyuan Zhu and Wenqiang Zhang and Zhenwu Cui and Tian Jia and Chaokun Li and Zhiyue Guo},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1939532},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1939532/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Preventive effects of compound probiotics supplementation on migraine: Mendelian randomization analysis and experimental evidence
AU  - Lu Bai
AU  - Qingteng Zhang
AU  - Jingyuan Zhu
AU  - Wenqiang Zhang
AU  - Zhenwu Cui
AU  - Tian Jia
AU  - Chaokun Li
AU  - Zhiyue Guo
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1939532
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1939532/full
AB  - Introduction: Migraine imposes a substantial economic and societal burden. The microbiota-gut-brain axis (MGBA) has emerged as a key potential mechanism, yet its causal relationships with migraine and the underlying pathways remain unclear.  Methods: We performed Mendelian randomization (MR) to assess the causal effects of gut microbiota on migraine, and further conducted mediation analysis to identify key mediating brain regions. In addition, we performed in vivo mouse experiments, in which we induced migraine-like pain via nitroglycerin (NTG) and investigated changes in gut microbiota, mechanical pain threshold, and regional brain activation following pretreatment with composite probiotics.  Results: MR analysis identified eight gut microbial taxa causally associated with migraine and its subtypes. Mediation analysis suggested that the association between genetically predicted Paraprevotella abundance and migraine risk was partially mediated by ICVF in the posterior insular cortex. In NTG-induced migraine mice, composite probiotics ameliorated gut dysbiosis and maintained Paraprevotella abundance, while elevating mechanical pain thresholds in both periorbital and hind paw region. Probiotics intervention also suppressed c-Fos expression in the pIC, Sp5c, PVT, and mPFC. Additionally, it specifically decreased CGRP immunoreactivity in the Sp5c.  Conclusion: This study provides genetic and experimental evidence supporting a potential role of the gut microbiome in migraine and the potential of microbiome-based strategies for migraine prevention.
SN  - 1664-302X
ER  -