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重复炎症性硬脑膜刺激引起的头部感觉异常导致大鼠肠道微生物组成的改变。

Repeated inflammatory dural stimulation-induced cephalic allodynia causes alteration of gut microbial composition in rats.

机构信息

Department of Neurology, the First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, 100853, Beijing, People's Republic of China.

Medical School of Chinese PLA, 100853, Beijing, People's Republic of China.

出版信息

J Headache Pain. 2022 Jun 25;23(1):71. doi: 10.1186/s10194-022-01441-9.

DOI:10.1186/s10194-022-01441-9
PMID:35752773
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9233368/
Abstract

BACKGROUND

Gut microbial dysbiosis and gut-brain axis dysfunction have been implicated in the pathophysiology of migraine. However, it is unclear whether migraine-related cephalic allodynia could induce the alteration of gut microbial composition.

METHODS

A classic migraine rat model was established by repeated dural infusions of inflammatory soup (IS). Periorbital mechanical threshold and nociception-related behaviors were used to evaluate IS-induced cephalic allodynia and the preventive effect of topiramate. The alterations in gut microbial composition and potential metabolic pathways were investigated based on the results of 16 S rRNA gene sequencing. Microbiota-related short-chain fatty acids and tryptophan metabolites were detected and quantified by mass spectrometry analysis.

RESULTS

Repeated dural IS infusions induced cephalic allodynia (decreased mechanical threshold), migraine-like behaviors (increased immobility time and reduced moving distance), and microbial composition alteration, which were ameliorated by the treatment of topiramate. Decreased Lactobacillus was the most prominent biomarker genus in the IS-induced alteration of microbial composition. Additionally, IS infusions also enhanced metabolic pathways of the gut microbiota in butanoate, propanoate, and tryptophan, while the increased tryptophan-related metabolites indole-3-acetamide and tryptophol in feces could be the indicators.

CONCLUSIONS

Inflammatory dural stimulation-induced cephalic allodynia causes the alterations of gut microbiota profile and microbial metabolic pathways.

摘要

背景

肠道微生物失调和肠-脑轴功能障碍与偏头痛的病理生理学有关。然而，目前尚不清楚偏头痛相关的头部感觉异常是否会引起肠道微生物组成的改变。

方法

通过重复硬膜内输注炎症汤（IS）建立经典偏头痛大鼠模型。眶周机械阈值和疼痛相关行为用于评估 IS 诱导的头部感觉异常以及托吡酯的预防作用。根据 16S rRNA 基因测序的结果，研究肠道微生物组成的变化和潜在的代谢途径。通过质谱分析检测和定量微生物群相关的短链脂肪酸和色氨酸代谢物。

结果

重复硬膜内 IS 输注可诱导头部感觉异常（机械阈值降低）、偏头痛样行为（不动时间增加和移动距离减少）和微生物组成改变，托吡酯治疗可改善这些改变。IS 诱导的微生物组成改变中，乳酸杆菌属减少是最显著的生物标志物属。此外，IS 输注还增强了肠道微生物群中丁酸盐、丙酸盐和色氨酸的代谢途径，而粪便中增加的色氨酸相关代谢物吲哚-3-乙酰胺和色醇可作为指标。

结论

炎症性硬脑膜刺激诱导的头部感觉异常导致肠道微生物群谱和微生物代谢途径的改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/3429ad281372/10194_2022_1441_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/2622a4f8c86c/10194_2022_1441_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/98b1b79dfb9a/10194_2022_1441_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/3429ad281372/10194_2022_1441_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/2622a4f8c86c/10194_2022_1441_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/7a0c2461cf5b/10194_2022_1441_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/54ea7970a63b/10194_2022_1441_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/98b1b79dfb9a/10194_2022_1441_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da56/9233368/3429ad281372/10194_2022_1441_Fig5_HTML.jpg

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