Pediatric acute-onset neuropsychiatric syndromes and the gut-oral-brain axis: a narrative review of emerging microbiome-immune interactions and therapeutic perspectives

Abstract

Background: Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by sudden-onset neuropsychiatric symptoms. Growing evidence indicates that gut and oral microbiota may contribute to disease pathogenesis through immune and inflammatory pathways.

Methods: This narrative review analyzed approximately 250 studies published between 2000 and 2024, retrieved from PubMed, Scopus, and Google Scholar. The selected works included clinical, immunological, and microbiome-related studies investigating the role of gut-oral-brain interactions in neuroinflammation or in pediatric PANS/PANDAS.

Findings: Alterations in gut and oral microbial communities appear to modulate neuroinflammation through increased intestinal and blood-brain barrier permeability, immune dysregulation, and altered production of neuroactive metabolites. Specific bacterial families, such as Bacteroidaceae, Rikenellaceae, and Odoribacteriaceae, have been associated with pro-inflammatory states, while oral pathogens may exacerbate systemic inflammation via the gut-oral-brain axis.

Conclusions: The reviewed evidence highlights the potential of microbiome-targeted strategies-including dietary modulation, probiotics, and anti-inflammatory approaches-as promising avenues for future personalized diagnosis and therapy in PANS/PANDAS. However, further controlled studies integrating microbial, immunological, and clinical data are required to confirm causal mechanisms and establish personalized therapeutic protocols.

Keywords: PANDAS; PANS; brain-gut axis; gastrointestinal microbiome; immunology; interleukin-17; microbiota; neuroinflammation.