An Altered Gut Microbiota–Brain Axis in Fragile X Syndrome May Explain Autistic Traits in Some Patients

The gut microbiota plays an essential role in human health, influencing gut–brain communication. Imbalances in this microbial ecosystem, termed dysbiosis, have been associated with increased gut permeability and gastrointestinal symptoms commonly reported in autism spectrum disorder (ASD), without implying a direct causal role in ASD itself. This study aimed to determine whether alterations in gut microbiota exist in individuals with Fragile X Syndrome (FXS), with or without ASD, compared to ASD patients and neurotypical controls, and to identify microbiota biomarkers associated with these disorders. Stool samples from Caucasian individuals aged 3–18 years belonging to four groups (ASD, FXS, FXS + ASD, and controls) were analysed by amplifying the V3–V4 region of the bacterial 16S rRNA gene to characterize microbiota composition. Significant differences were found among patient groups compared to neurotypical controls, with notable similarities between the ASD and FXS + ASD groups. Additionally, specific microbiota biomarkers were identified for each patient group. These findings suggest that distinct microbiota alterations are associated with FXS and ASD, which may contribute to a more accurate characterization of symptoms in these disorders and could serve as potential biomarkers for assessing neurodevelopmental risk.