Serum Metabolic and Gut Microbiome Differences in Age-Associated Fragile X Syndrome (FXS) Pediatric Patients May Benefit Clinical Therapy Development.

Background: Fragile X syndrome (FXS) is a rare, genetically based neurodevelopmental disorder characterized by intellectual disability. While previous research has largely focused on its genetic mechanisms, the role of metabolism and the gut microbiome in FXS remains underexplored. This study aimed to investigate age-related metabolic differences in the gut flora and serum metabolites of children with FXS and their associations with clinical behavioral outcomes.

Methods: A total of 32 children with FXS under 18 years were enrolled and divided into two age groups: younger (3-8 years) and older (8-18 years). Intestinal microbiota composition was analyzed using 16S rDNA gene sequencing, and serum metabolite profiles were assessed via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Spearman correlation analysis was used to assess associations among gut flora, serum metabolites, and scores from the Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL).

Results: Significant differences in gut bacterial genera and 1,352 serum metabolites were observed between the age groups. The older group exhibited higher levels of phospholipids, steroids, and peptides, and enrichment in the steroid hormone biosynthesis pathway. Several metabolites were significantly correlated with SRS and CBCL scores, indicating potential links between metabolic changes and behavioral symptoms.

Conclusion: Age-associated metabolic and gut microbiota alterations in FXS may contribute to variations in clinical presentation. These findings suggest a metabolic basis for FXS and provide a foundation for future research into microbiome-targeted interventions in FXS management.