Design: Prospective (N=126) + RCT Pilot (N=23) + In vivo (Rats)
Population: Pediatric (6-19 yrs), with/without GI disorders
Intervention: 12 weeks, B. longum vs Active control (BbLa)
Key method: 16S rRNA sequencing + CGRP/c-Fos analysis
1. Microbial "fingerprint" of risk
Migraine patients show critical B. longum deficiency. Presence of GI disorders (46.8% of cohort) correlates with aggressive flora.
*LDA Score > 4.0. Comparison: Healthy vs Migraine. 16S rRNA data.
2. Clinical efficacy (RCT)
-65%
Headache days
(by week 12)
0.014
P-value
(B. longum vs Control)
None
Effect in control
group (BbLa)
Specificity insight: Attack frequency reduction observed only in B. longum group. Standard probiotic group (B. bifidum/L. acidophilus) showed no improvement.
3. Mechanism of action
Gut-brain axis restoration through reduced neuroinflammation (CGRP) and trigeminal nerve activation.
In vivo data: c-Fos suppression in TCC and CGRP in TG.
Key takeaway: Not all probiotics are created equal. Study reveals a "therapeutic window": B. longum acts as precision neuromodulator, reducing CGRP-dependent trigeminal nerve activation. Effect absent in related strains, opening path to creating "psychobiotics" class for treatment-resistant pediatric migraine.