Gut Microbiota and Amino Acid Profiles in Febrile Seizures: A Comprehensive Analysis

Abstract Febrile seizures (FS) are the most common neurological emergency in early childhood.Emerging evidence suggests a role for the gut–brain axis in FS pathogenesis. However, their underlying mechanisms remain poorly understood. We analyzed gut microbiota composition via 16S rRNA gene sequencing and serum amino acid profiles using ion exchange chromatography in 50 patients with FS and 50 healthy controls.Our findings reveal that children with FS had a lower diversity of gut microbiota than healthy controls, with increases in Streptococcus, Enterococcus, and Escherichia–Shigella and decreases in beneficial bacteria such as Faecalibacterium, Lachnoclostridium, and Parasutterella. Sera of children with FS showed higher levels of phenylalanine, kynurenine, and γ-aminobutyric acid (GABA) and lower levels of tryptophan, threonine, and lysine than those of healthy controls. Bacteria–metabolite correlation analysis revealed that Lachnoclostridium and Parasutterella were strongly associated with phenylalanine and kynurenine.Our findings indicate that gut dysbiosis and disturbances of amino acid metabolism play a critical role in the pathogenesis of FS, suggesting potential therapeutic targets. Specifically, the reduction of Lachnoclostridium and Parasutterella, coupled with altered levels of phenylalanine, kynurenine, and GABA, significantly contributes to FS development. These changes may disrupt neurotransmitter signaling, leading to increased neuronal excitability and heightened seizure susceptibility.