Tryptophan metabolites and gut microbiota play an important role in pediatric migraine diagnosis

J Headache Pain. 2024 Jan 5;25(1):2. doi: 10.1186/s10194-023-01708-9.

Abstract

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).

Keywords: Diagnostic biomarkers; Gut microbiota; Pediatric migraine; Tryptophan metabolism.

MeSH terms

  • Biomarkers
  • Child
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Kynurenic Acid
  • Migraine Disorders* / diagnosis
  • Quinolinic Acid
  • Tryptophan / metabolism

Substances

  • Tryptophan
  • Kynurenic Acid
  • Quinolinic Acid
  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT05969990