色氨酸代谢物和肠道微生物群在儿童偏头痛的诊断中起着重要作用。
Tryptophan metabolites and gut microbiota play an important role in pediatric migraine diagnosis.
机构信息
Department of Pediatrics, Qilu Hospital of Shandong University, No.107 West Wenhua Road, Jinan, 250012, Shandong Province, China.
Shandong First Medical University Affiliated Provincial Hospital, Huaiyin Distinct, Jingwuweiliu Road, Jinan, 250021, Shandong Province, China.
出版信息
J Headache Pain. 2024 Jan 5;25(1):2. doi: 10.1186/s10194-023-01708-9.
BACKGROUND
The pathogenesis of pediatric migraine remains unclear and presents challenges in diagnosis. Recently, growing evidence has indicated that the gut microbiota can exert modulatory functions at the gut-brain axis by directly or indirectly regulating tryptophan metabolism. Consequently, we aimed to elucidate the potential association among gut microbiota, tryptophan metabolism, and pediatric migraine while also identifying diagnostic biomarkers for pediatric migraine.
METHODS
The gut microbiota composition of 33 migraine children and 42 healthy children, aged less than ten years, from the GMrepo database, was analyzed using the Shannon index, Simpson index, principal coordinates analysis, and Wilcoxon rank-sum test. Microbial diagnostic biomarkers were identified using linear discriminant analysis effect size, ridge regression, and random forest. Plasma concentrations of tryptophan metabolites investigated by enzyme-linked immunosorbent assay were compared between 51 migraine children and 120 healthy children, aged less than eighteen years, using t tests and analysis of variance. The receiver operating characteristic curve was performed to evaluate the diagnostic value of microbial and metabolite biomarkers in pediatric migraine.
RESULTS
Differences in the composition of gut microbiota, notably the genera that regulate tryptophan metabolism, were observed in pediatric migraine children. Further investigations revealed a significant decrease in plasma kynurenic acid levels (p < 0.001) among migraine children, along with a significant increase in serotonin (p < 0.05) and quinolinic acid (p < 0.001). Subsequently, we established the normal reference intervals for plasma concentrations of tryptophan metabolites in children. More importantly, the ratio of kynurenic acid to quinolinic acid (AUC: 0.871, sensitivity: 86.3%, specificity: 83.3%) exhibited excellent diagnostic efficacy for pediatric migraine.
CONCLUSION
Our study suggests that the gut microbiota may play an important role in the development of pediatric migraine by regulating tryptophan metabolism. We believe that microbial and metabolite biomarkers are sensitive diagnostic tests for pediatric migraine.
TRIAL REGISTRATION
The study was registered at ClinicalTrials.gov (NCT05969990).
背景
儿科偏头痛的发病机制尚不清楚，其诊断具有挑战性。最近，越来越多的证据表明，肠道微生物群可以通过直接或间接调节色氨酸代谢在肠-脑轴发挥调节作用。因此，我们旨在阐明肠道微生物群、色氨酸代谢与儿科偏头痛之间的潜在关联，并确定儿科偏头痛的诊断生物标志物。
方法
我们分析了 GMrepo 数据库中 33 名偏头痛儿童和 42 名健康儿童（年龄均小于 10 岁）的肠道微生物群组成，使用 Shannon 指数、Simpson 指数、主坐标分析和 Wilcoxon 秩和检验进行分析。使用线性判别分析效应大小、岭回归和随机森林识别微生物诊断生物标志物。采用 t 检验和方差分析比较了 51 名偏头痛儿童和 120 名健康儿童（年龄均小于 18 岁）的色氨酸代谢物的血浆浓度。采用受试者工作特征曲线评估微生物和代谢物生物标志物在儿科偏头痛中的诊断价值。
结果
我们发现儿科偏头痛儿童的肠道微生物群组成存在差异，特别是调节色氨酸代谢的属存在差异。进一步的研究表明，偏头痛儿童的血浆犬尿氨酸酸水平显著降低（p<0.001），而血清素（p<0.05）和喹啉酸（p<0.001）水平显著升高。随后，我们建立了儿童血浆色氨酸代谢物浓度的正常参考区间。更重要的是，犬尿氨酸酸与喹啉酸的比值（AUC：0.871，敏感性：86.3%，特异性：83.3%）对儿科偏头痛具有极好的诊断效能。
结论
我们的研究表明，肠道微生物群可能通过调节色氨酸代谢在儿科偏头痛的发展中发挥重要作用。我们认为微生物和代谢物生物标志物是儿科偏头痛敏感的诊断测试。
试验注册
该研究在 ClinicalTrials.gov 注册（NCT05969990）。
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