Metataxonomic and Immunological Analysis of Feces from Children with or without Phelan-McDermid Syndrome

Abstract

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by a developmental delay and autism spectrum disorder (ASD)-like behaviors. Emerging research suggests a link between gut microbiota and neuropsychiatric conditions, including PMS. This study aimed to investigate the fecal microbiota and immune profiles of children with PMS compared to healthy controls. Fecal samples were collected from children diagnosed with PMS and age-matched healthy controls. The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) were quantified through gas chromatography. Immunological profiling was conducted using a multiplex cytokine assay. Significant differences were observed in the gut microbiota composition between PMS patients and controls, including a lower abundance of key bacterial genera such as Faecalibacterium and Agathobacter in PMS patients. SCFA levels were also reduced in PMS patients. Immunological analysis revealed higher levels of several pro-inflammatory cytokines in the PMS group, although these differences were not statistically significant. The findings indicate that children with PMS have distinct gut microbiota and SCFA profiles, which may contribute to the gastrointestinal and neurodevelopmental symptoms observed in this syndrome. These results suggest potential avenues for microbiota-targeted therapies in PMS.

Keywords: Phelan–McDermid syndrome; autism spectrum disorder; feces; immunoprofiling; microbiota; short-chain fatty acids.

Figure 1

Metataxonomic profiles of fecal samples of healthy controls (Control; orange), and patients with Phelan–McDermid syndrome (PMS; pink). (a) Comparison of alpha diversity at the ASV level calculated using the Shannon index between both groups of patients. (b) Comparison of alpha diversity at the ASV level calculated using the Simpson index between the groups. Principal coordinate analysis (PCoA) plots of bacterial profiles at the genus level based on (c) the Bray–Curtis dissimilarity index in each group and (d) Jaccard’s coefficient for binary data (presence or absence). The values on each axis label in graphs (c,d) represent the percentage of the total variance explained by that axis.