The Gut–Brain Axis in Migraine: Insights from Preclinical Animal Models
Abstract
Migraine is a prevalent and disabling neurological disorder whose pathophysiology extends beyond the central nervous system and involves complex interactions among neural, immune, endocrine, and gastrointestinal pathways. Increasing evidence from preclinical studies suggests that the gut–brain axis plays a critical role in migraine through mechanisms such as gut microbiota dysbiosis, impaired intestinal barrier function, neuroinflammation, immune activation, microbial metabolite signaling, and alterations in neurotransmitter regulation. However, findings from animal studies remain scattered across diverse experimental models and mechanistic frameworks. This systematic review aims to comprehensively identify, evaluate, and synthesize evidence from in vivo animal studies investigating the relationship between the gut–brain axis and migraine. The review will examine gut-related mechanisms and interventions, including microbiota alterations, intestinal permeability, inflammatory pathways, microbial metabolites, and microbiome-targeted therapies, within validated experimental models of migraine. Methodological quality and risk of bias will be assessed using established tools for animal research. This review is expected to provide a comprehensive overview of current preclinical evidence, clarify key mechanistic pathways linking the gut–brain axis to migraine, identify knowledge gaps, and highlight potential targets for future translational and clinical research.
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