偏头痛患者肠道菌群对硬脑膜淋巴管及脑结构和功能的影响

偏头痛是50岁以下人群中的首位失能性疾病，机制不清。我们前期工作发现偏头痛患者的肠道菌群构成与健康对照有明显差异，肠道菌群代谢物色氨酸、犬尿氨酸、丁酸等显著低于健康人，这三者均参与中枢及外周免疫系统调节，它们从外周作用于中枢的路径不明。近年发现的硬脑膜淋巴管是脑内大分子物质的清除途径，是脑脊液回流的另一通路。我们在前期研究中发现偏头痛关键调制物质降钙素基因相关肽和垂体腺苷酸环化酶激活肽的阳性纤维与硬脑膜淋巴管伴行，解剖关系密切。据此，我们推测脑-硬脑膜淋巴管-肠道菌群发生相互作用参与偏头痛的发生。为此我们拟从头痛行为学、脑片电生理、活体小动物成像、转录组学、代谢组学等方面观察偏头痛肠道菌群是否使小胶质细胞和硬脑膜淋巴管出现结构异常、功能紊乱、动物头痛易感性增强。在国际上首次探讨偏头痛的病理过程与硬脑膜淋巴管的关系，从全新角度探索脑-肠轴神经免疫调节参与偏头痛的可能机制。

According to the WHO report, migraine is first cause of disability in under 50s. The pathophysiology of migraine is still unclear. We found that the composition of gut microbiota in migraineurs was different from the healthy people, and the microbial metabolites tryptophan, kynurenine, and butyrate were statistically lower. Those microbial metabolites participated the modulation in central and peripheral immune system, however, the route where they act on the central from the peripheral is not clear. Recently, dural lymphatic vessels were found the path.for macromolecule clearance in the brain and the other route for cerebral spinal fluid recirculation. We found that calcitonin gene–related peptide and pituitary adenylyl cyclase activating peptide positive nerve fibers co-express with lymphatic vessels on the dura. Above all, we speculate that brain-dural lymphatic vessel-gut microbiota interaction together involve in the migraine pathophysiology. To prove that, we use headache behavioral analysis, brain slice eletrophysiological study, in vivo imaging, transcriptome, Metabolomic techniques to research the relationship between gut microbiota, microglial cells in brain and the dural lymphatic vessels. We will be the first who try to explore the.relationship of meningeal lymphatic vessels and migraine mechanisms, and try to discuss the neuro-immune modulation of brain-gut axis in the migraine process from a brand new sight.