Fecal amino acid and short-chain fatty acid profiles in children with migraine: a targeted metabolomics study

Abstract

Background – Research has primarily focused on the gut microbiota of adult migraine patients; however, investigations into specific metabolic alterations in pediatric migraine remain limited, and comprehensive targeted metabolomics characterization in this population is still lacking. This exploratory cross-sectional study aims to identify specific metabolic signatures associated with pediatric migraine using targeted metabolomics. Methods – We enrolled 30 children with migraine and 30 healthy controls (with no history of headache) aged 5–14 years from Hebei Province, China, and collected 60 fresh fecal samples. Using targeted metabolomics, we profiled amino acids, their derivatives, and short-chain fatty acids (SCFAs) to compare fecal metabolite profiles between groups. Differentially altered metabolites were further analyzed through KEGG pathway enrichment and receiver operating characteristic (ROC) curve analysis. Results – Compared with healthy controls, eight amino acid metabolites—including 2, 6-diaminopimelic acid, L-valine, L-leucine, and L-phenylalanine—were significantly elevated in children with migraine (P < 0.05). These differential metabolites were enriched in pathways related to the biosynthesis and degradation of valine, leucine, and isoleucine; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and arginine biosynthesis. SCFA-related differences were also observed between groups; however, most individual SCFA comparisons did not reach statistical significance and should therefore be interpreted cautiously. Some of these differential metabolites were also mapped to pathways related to protein digestion and absorption. ROC curve analysis showed that tryptamine (AUC = 0.70, 95% CI: 0.56–0.84) and 2, 6-diaminopimelic acid (AUC = 0.73, 95% CI: 0.60–0.87) had modest discriminative performance in distinguishing children with migraine from healthy controls. Conclusion – Children with migraine exhibit distinct metabolic signatures, particularly involving amino acid-related metabolites. The abnormal elevation of key amino acids, such as phenylalanine and tryptophan, was associated with pediatric migraine. SCFA-related differences were also observed. Furthermore, metabolites such as tryptamine and 2, 6-diaminopimelic acid may represent candidate metabolites with preliminary discriminatory value for pediatric migraine, warranting further investigation in larger validation cohorts.