Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role of Bifidobacterium longum.

Migraine is a disabling neurological disorder that often begins in childhood or adolescence and is frequently accompanied by gastrointestinal (GI) symptoms. However, the microbiota signatures and gut-brain interactions underlying pediatric migraine, particularly in the presence of GI disorder, remain poorly defined. This study aimed to explore the clinical and microbial features of pediatric migraine, as well as the therapeutic potential of probiotics.We prospectively enrolled 126 pediatric migraine patients (ages 6-19) with or without GI disorder and 50 age-matched healthy controls. Fecal microbiota was profiled using 16S rRNA sequencing. Patients with migraine were stratified based on Rome IV-defined GI disorders and evaluated for headache characteristics, PedMIDAS scores (disability assessment), plasma calcitonin gene related peptide (CGRP, thought as a key biomarker of migraine), cytokines, and fecal calprotectin. Probiotic effects were tested in both young (3-4 weeks) and adult capsaicin-induced migraine rat models, and an exploratory pilot study involving 23 pediatric migraine patients.Compared to controls, migraine patients exhibited distinct gut microbiota with reduced Bifidobacterium longum. and elevated Bacteroides. GI disorders were present in 46.8% of migraine patients and were associated with significantly higher rates of abdominal pain (50% vs. 13%, p <0.001), greater migraine-related disability (PedMIDAS: 60 ± 13.2 vs. 29 ± 7.0, p = 0.042), elevated fecal calprotectin, and enrichment of Streptococcus gallolyticus. In contrast, Faecalibacterium prausnitzii, positively correlated with B. longum, was linked to milder symptoms and shorter disease duration in migraine patients without GI disorder. In animal models, B. longum attenuated trigeminal activation in both young and adult rats. An exploratory pilot study showed B. longum supplementation led to reductions in headache days, intensity, and frequency. These findings reveal distinct gut microbial signatures in pediatric migraine, and identify B. longum as a promising microbiota-targeted therapeutic strategy. Our work highlights the therapeutic potential of modifying the gut-brain axis in childhood migraine.