Changes of serum metabolomics and gut microbiota reveal specific characteristics of children with febrile seizures

Abstract

Background and purpose: Febrile seizures (FS) pose a severe threat to the neurological development of children. Probing the abnormality of host metabolism is essential for the prevention, diagnosis, and treatment of FS.

Methods: Based on clinically collected serum and fecal samples, we used nontargeted metabolomics and 16S rDNA sequencing to explore the relationship of serum metabolite levels and gut microbiota community with the occurrence of FS.

Results: Metabolomic analysis revealed abnormalities in multiple metabolic pathways in serum of FS patients, such as tryptophan metabolism and steroid hormone biosynthesis. Intestinal flora analysis indicated that the α-diversity of gut microbiota in FS patients was significantly reduced. In addition, the relative abundance of a variety of bacteria at the phylum level was remarkably changed in patients with FS, including decreased Firmicutes and Verrucomicrobia. Eleven serum metabolites were identified to be biomarker candidates for FS diagnosis. With the help of a panel biomarker strategy combining four biomarkers as a cluster, four bacteria (i.e., Rothia, Coprococcus, Lactobacillus, and Oscillospira) in a defined panel displayed perfect differentiation of subtypes of FS.

Conclusions: Combining metabolomic and intestinal flora analysis revealed specific characteristics of children with FS, and provided new clues for the diagnosis of FS and the classification of seizure types. In summary, these findings may provide new insights into revealing the significance of serum metabolites and gut microbiota in the pathogenesis of FS.

Keywords: febrile seizures; gut microbiota; metabolic pathway; metabolomics; omics analysis.