Integrated Multiomics Reveals Gut–Brain Axis Dysregulation and Phenotype-Specific Metabolic Signatures in Children with Febrile Seizures
Abstract
Background: Febrile seizures (FSs) are the most common neurological emergency in early childhood; however, the biological basis of disease heterogeneity remains poorly understood. Although growing evidence suggests that gut–brain axis dysregulation contributes to seizure susceptibility, it remains unclear whether gut microbiota-associated metabolic disturbances are linked to clinical phenotypes, particularly simple FS (SFS) and complex FS (CFS). Methods: An integrated multiomics study was conducted in clinically characterized pediatric cohorts, comprising 50 children with FS and 50 healthy controls, and their gut microbiota was profiled via 16S rRNA sequencing. As some pediatric serum specimens did not meet the minimum volume requirement of the analytical platform, serum amino acid profiling was performed in a subset of samples using an equal-volume pooling strategy. In brief, two individual serum samples from the same study group were combined into one composite sample, yielding 25 pooled samples in the FS group and 25 in the control group. Subsequently, untargeted fecal metabolomics was performed in an expanded cohort of 53 healthy controls, 50 children with SFS, and 42 children with CFS. Additionally, the central metabolic profiles of the CFS and SFS groups were compared using untargeted cerebrospinal fluid metabolomics. Given the variation in sample sizes across omics platforms, each dataset was analyzed within its corresponding eligible subset, and cross-omics…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 50 participants or records.
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