Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut–Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

SUMMARY

This study investigated whether children with PANDAS, a subset of Pediatric Acute Neuropsychiatric Syndrome (PANS), exhibit alterations in the gut microbiome and associated metabolic pathways that could contribute to neuropsychiatric symptoms through the gut–brain axis. Using a multi-omics approach that combined microbial sequencing, metagenomic analysis, and metabolomic profiling, researchers analyzed stool, nasal, and throat samples from children with PANDAS and healthy controls, including several twin pairs discordant for the condition. While nasal and throat microbial communities showed relatively few differences, the gut microbiome of children with PANDAS demonstrated significant changes in both composition and function.

Children with PANDAS had reduced gut microbial diversity and a marked loss of several bacterial species commonly associated with intestinal barrier integrity, immune regulation, and production of beneficial metabolites. At the same time, the investigators observed increased abundance of microbial species linked to inflammatory processes and altered immune responses. Functional analysis suggested widespread reductions in microbial genes involved in metabolic activity, bacterial communication, and neurotransmitter-related pathways. Notably, pathways involved in gamma-aminobutyric acid (GABA) production and glutamate metabolism were disrupted, raising the possibility that microbiome alterations may influence neurological function through changes in neuroactive compounds.

Metabolomic analysis further demonstrated that children with PANDAS possessed distinct fecal metabolic profiles compared with healthy controls. Alterations were observed in amino acid metabolism, bile acid pathways, lipid signaling molecules, and other metabolites with known relevance to immune regulation and nervous system function. Integration of microbiome and metabolomic data revealed disrupted networks connecting microbial activity to metabolic signaling pathways involved in gut–brain communication. Although the study was limited by a relatively small sample size and cannot establish causation, the findings provide evidence that gut microbial dysbiosis and altered microbial metabolism may contribute to immune and neuropsychiatric dysfunction in PANDAS. These results support further investigation of the gut–brain axis as a potential source of biomarkers and future therapeutic targets for children affected by PANDAS.

LINK TO PAPER: https://doi.org/10.3390/microorganisms14051036