Work

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

Year: 2026

Type: article

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.

Source: Frontiers in Microbiology

DOI: 10.3389/fmicb.2026.1939532