Probiotic modulation of central and peripheral sensitization in a migraine model via the gut-brain-trigeminal axis.

2025-11-20
Scientific reports 15(1)

PubMed: 41266742
DOI: 10.1038/s41598-025-24928-2

Study Design

Population: rat model of cortical spreading depression (CSD)
Methods: targeted probiotic supplementation-Lactobacillus plantarum, Bifidobacterium longum, their combination, and a multi-strain formulation (Pro-14)

Rigorous Journal
Animal Study

The gut-brain axis has emerged as a pivotal modulator of migraine pathophysiology. This study examined the neurophysiological effects of targeted probiotic supplementation-Lactobacillus plantarum, Bifidobacterium longum, their combination, and a multi-strain formulation (Pro-14)-in a rat model of cortical spreading depression (CSD), a hallmark trigger of migraine. B.longum significantly reduced CSD frequency (p = 0.0045), while L.plantarum and its combination with B.longum markedly attenuated CSD amplitude (p = 0.0003, p = 0.01, respectively), reflecting suppression of cortical hyperexcitability. In small-to-medium-sized trigeminal ganglion (TG) neurons, probiotics significantly lowered total spike counts (p < 0.0001), and induced hyperpolarization of resting membrane potential (p < 0.0001), consistent with peripheral desensitization. Additionally, the threshold-Resting Membrane Potential (RMP) gap increased significantly across all treated groups (p < 0.0001), indicating reduced neuronal excitability. Only B.longum prolonged action potential duration and depolarization time (p = 0.0454 and p = 0.034, respectively), suggesting enhanced modulation of nociceptive signaling. In large-sized TG neurons, similar hyperpolarizing trends in RMP (p < 0.0001) and increased excitability thresholds (p < 0.0001) were observed without changes in spike frequency. These findings reveal strain-specific modulation of central and peripheral sensitization via the gut-brain-trigeminal axis and support the development of precision-targeted, microbiota-based therapies as non-pharmacologic strategies for migraine prophylaxis.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bifidobacterium plantarum	—	Increased Neuronal Firing Threshold	Beneficial	Large	View source Additionally, the threshold-Resting Membrane Potential (RMP) gap increased significantly across all treated groups (p < 0.0001), indicating reduced neuronal excitability.
Bifidobacterium plantarum	—	Modulated Nociceptive Signaling	Beneficial	Small	View source Only B.longum prolonged action potential duration and depolarization time (p = 0.0454 and p = 0.034, respectively), suggesting enhanced modulation of nociceptive signaling.
Bifidobacterium plantarum	—	Reduced Cortical Spreading Depression	Beneficial	Moderate	View source B.longum significantly reduced CSD frequency (p = 0.0045), while L.plantarum and its combination with B.longum markedly attenuated CSD amplitude (p = 0.0003, p = 0.01, respectively), reflecting suppression of cortical hyperexcitability.
Bifidobacterium plantarum	—	Reduced Trigeminal Neuron Excitability	Beneficial	Moderate	View source In small-to-medium-sized trigeminal ganglion (TG) neurons, probiotics significantly lowered total spike counts... and induced hyperpolarization of resting membrane potential... Additionally, the threshold-Resting Membrane Potential (RMP) gap increased significantly across all treated groups... indicating reduced neuronal excitability.