Pediatric Acute-onset Neuropsychiatric Syndromes (PANS/PANDAS) and the Gut-Oral-Brain Axis: A Narrative Review of Emerging Microbiome-Immune Interactions and Therapeutic Perspectives

Mariarosaria Matera^1,2Valentina Biagioli^3,4*Maria Teresa Illiceto⁵Chiara Maria Palazzi²Ilaria Cavecchia^4,6Andrea Manzi⁷Sebastian Lugli⁸Laura Pennazzi⁹Martina Meocci¹⁰Fausto Pedaci¹¹Alexander Bertuccioli^12,4

• ¹Department of Pediatric Emergencies, Misericordia Hospital, Grosseto, Italy, Grosseto, Italy
• ²Microbiota International Clinical Society (MICS), 10123 Turin, Italy, Torino, Italy
• ³Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy, Genova, Italy
• ⁴Microbiota International Clinical Society (MICS), 10123 Turin, Italy, Turin, Italy
• ⁵Department of Pediatrics- Unit of Pediatric Gastroenterology and Endoscopy, Santo Spirito Hospital, Pescara, Italy, 65121, Italy
• ⁶Microbiomic Department, Koelliker Hospital, 10134 Turin, Italy, Turin, Italy
• ⁷Director of Pediatrics, Pozzuoli Hospital, Pozzuoli, Italy
• ⁸Ordinary member of Microbiota International Clinical Society (MICS),, Turin, Italy
• ⁹Italian Society of Nutraceuticals (SINut), 40100 Bologna, Italy, Bologna, Italy
• ¹⁰Department of Respiratory Medicine, University of Siena, Siena, Italy, Siena, Italy
• ¹¹Department of Pediatrics, Valdarno Hospital, Montevarchi, Arezzo, Italy, Arezzo, Italy
• ¹²Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029, Urbino, Italy, urbino, Italy

Background: Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are This is a provisional file, not the final typeset article 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.