Frontiers in immunology · 2025
Pediatric acute-onset neuropsychiatric syndromes and the gut-oral-brain axis: a narrative review of emerging microbiome-immune interactions and therapeutic perspectives.
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Matera Mariarosaria, Biagioli Valentina, Illiceto Maria Teresa, Palazzi Chiara Maria, Cavecchia Ilaria, Manzi Andrea, Lugli Sebastian, Pennazzi Laura, Meocci Martina, Pedaci Fausto Andrea, Bertuccioli Alexander
Аннотация
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.
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.