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<p>The gut–brain axis has emerged as a pivotal modulator of migraine pathophysiology. This study examined the neurophysiological effects of targeted probiotic supplementation—<i>Lactobacillus plantarum</i>, <i>Bifidobacterium longum</i>, their combination, and a multi-strain formulation (Pro-14)—in a rat model of cortical spreading depression (CSD), a hallmark trigger of migraine. <i>B.longum</i> significantly reduced CSD frequency (<i>p</i> = 0.0045), while <i>L.plantarum</i> and its combination with <i>B.longum</i> markedly attenuated CSD amplitude (<i>p</i> = 0.0003, <i>p</i> = 0.01, respectively), reflecting suppression of cortical hyperexcitability. In small-to-medium–sized trigeminal ganglion (TG) neurons, probiotics significantly lowered total spike counts (<i>p</i> &lt; 0.0001), and induced hyperpolarization of resting membrane potential (<i>p</i> &lt; 0.0001), consistent with peripheral desensitization. Additionally, the threshold–Resting Membrane Potential (RMP) gap increased significantly across all treated groups (<i>p</i> &lt; 0.0001), indicating reduced neuronal excitability. Only <i>B.longum</i> prolonged action potential duration and depolarization time (<i>p</i> = 0.0454 and <i>p</i> = 0.034, respectively), suggesting enhanced modulation of nociceptive signaling. In large-sized TG neurons, similar hyperpolarizing trends in RMP (<i>p</i> &lt; 0.0001) and increased excitability thresholds (<i>p</i> &lt; 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Phichaya Suthivanich,
  • Sirikorn Vongseenin,
  • Vichaya Auvichayapat,
  • Weera Supronsinchai,
  • Somying Tumwasorn,
  • Maneerat Chayanupatkul,
  • Saknan Bongsebandhu-phubhakdi

摘要

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.