Febrile seizure (FS) is a highly recurrent neuro-system disorder in children that affects their nervous system development and quality of life. However, the pathogenesis of febrile seizures remains unclear. Our study aims to investigate the potential differences in the intestinal flora and metabolomics between healthy children and those with FS. By examining the relationship between specific flora and different metabolites, we hope to shed light on the pathogenesis of FS. Fecal specimens were collected from healthy children (n = 15) and children with febrile seizures (n = 15), and 16S rDNA sequencing was conducted to characterize intestinal flora. Subsequently, fecal samples from healthy (n = 6) and febrile seizure children (n = 6) were used to characterize metabolomics using linear discriminant analysis of effect size, orthogonal partial least squares discriminant analysis, Kyoto Encyclopedia of Genes and Genomes (pathway enrichment analysis), and Kyoto encyclopedia of genes and genomes topology analysis. Liquid chromatography-mass spectrometry was used to identify metabolites in the fecal samples. The intestinal microbiome in the febrile seizure children significantly differed from that in the healthy children at the phylum level. Ten differentially accumulated metabolites (xanthosine, (S)-abscisic acid, N-palmitoylglycine, (+/-)-2-(5-methyl-5-vinyl-tetrahydrofuran-2-yl) propionaldehyde, (R)-3-hydroxybutyrylcarnitine, lauroylcarnitine, oleoylethanolamide, tetradecyl carnitine, taurine, and lysoPC [18:1 (9z)/0:0] were considered the potential febrile seizure markers. Three metabolic pathways (taurine metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis) were found essential in febrile seizure. Bacteroides were significantly correlated with the 4 differential metabolites. Adjusting the balance of intestinal flora may be an effective method for preventing and treating febrile seizures.
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