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

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.

• Publication year

  2025

• Venue

  Frontiers in Immunology

• Publication date

  2025-11-27

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3389/fimmu.2025.1726630PMID 41394880PMCID 12695544
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases

  2025cited by this paper
• Recent advances of engineered probiotics for therapeutic applications

  2025cited by this paper
• The relationship between increased levels of microbiota-derived lipopolysaccharide in obesity and the pathophysiology of neurodegenerative diseases.

  2025cited by this paper
• Description of the draft genome sequence of Streptococcus salivarius eK12, a derivative of the probiotic strain Streptococcus salivarius K12 with a modified plasmid

  2025cited by this paper
• Gut inflammation promotes microbiota-specific CD4 T cell-mediated neuroinflammation

  2025cited by this paper
• A role for microglia in mediating the microbiota–gut–brain axis

  2025cited by this paper
• Add-on probiotics for inflammatory depression - A double-blind randomized placebo-controlled trial.

  2025cited by this paper
• Adjunctive use of Streptococcus salivarius M18 probiotic in the treatment of periodontitis: a randomized controlled trial

  2025cited by this paper
• Gut microbiome, a potential modulator of neuroepigenome.

  2025cited by this paper
• Case Report: Special recoveries from major mental illness in childhood: a case series

  2025cited by this paper
• Assessing the nutritional quality of gluten-free packaged foods for children

  2025cited by this paper
• Influence of Inflammation, Gut Microbiota, and Stress on Cognition and Oral Health Therapies.

  2025cited by this paper
• Beyond the Gut: Unveiling Butyrate’s Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review

  2025cited by this paper
• Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

  2025cited by this paper
• Bifidobacterium adolescentis PRL2019 in Pediatric Irritable Bowel Syndrome: A Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial

  2025cited by this paper
• Advances in intestinal epithelium and gut microbiota interaction

  2025cited by this paper
• Interactions of human milk oligosaccharides with the immune system

  2025cited by this paper
• From bugs to brain: unravelling the GABA signalling networks in the brain–gut–microbiome axis

  2024influential reference
• IL-17 in serum and cerebrospinal fluid of pediatric patients with acute neuropsychiatric disorders: Implications for PANDAS and PANS.

  2024cited by this paper
• Occupational performance patterns in children with paediatric acute‐onset neuropsychiatric syndrome

  2024cited by this paper
• IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures

  2024cited by this paper
• Balancing the Oral–Gut–Brain Axis with Diet

  2024cited by this paper
• The Kynurenine Pathway in Gut Permeability and Inflammation

  2024cited by this paper
• Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities

  2024cited by this paper
• The microbiota: a crucial mediator in gut homeostasis and colonization resistance

  2024cited by this paper
• Role of short chain fatty acids on astrocytes and microglia in Alzheimer's disease brain

  2024cited by this paper
• Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.

  2024cited by this paper
• Examining immune-inflammatory mechanisms of probiotic supplementation in depression: secondary findings from a randomized clinical trial

  2024cited by this paper
• Gluten-containing flours and gluten-free flours as a source of calcium, magnesium, iron and zinc

  2024cited by this paper
• Short-chain fatty acids: linking diet, the microbiome and immunity

  2024cited by this paper
• Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.

  2024cited by this paper
• Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

  2024cited by this paper
• Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population

  2024cited by this paper
• Potential of fermented foods and their metabolites in improving gut microbiota function and lowering gastrointestinal inflammation

  2024cited by this paper
• Sensory processing in children with Paediatric Acute-onset Neuropsychiatric Syndrome.

  2024cited by this paper
• Brain-derived neurotrophic factor levels across psychiatric disorders: A systemic review and network meta-analysis.

  2024cited by this paper
• Mitochondrial Dysfunction in Periodontitis and Associated Systemic Diseases: Implications for Pathomechanisms and Therapeutic Strategies

  2024cited by this paper
• Engineered probiotic overcomes pathogen defences using signal interference and antibiotic production to treat infection in mice

  2024cited by this paper
• Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach.

  2024cited by this paper
• Communication of gut microbiota and brain via immune and neuroendocrine signaling

  2023cited by this paper
• Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells

  2023cited by this paper
• Advances in the study of IL-17 in neurological diseases and mental disorders

  2023cited by this paper
• Neuroinflammation in the Brain and Role of Intestinal Microbiota: An Overview of the Players.

  2023cited by this paper
• Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder

  2023cited by this paper
• The Gluten-Free Diet for Celiac Disease: Critical Insights to Better Understand Clinical Outcomes

  2023cited by this paper
• Bifidobacterium breve PRL2020: Antibiotic-Resistant Profile and Genomic Detection of Antibiotic Resistance Determinants

  2023cited by this paper
• Randomized Clinical Trial of Oral Probiotic Streptococcus salivarius M18 on Salivary Streptococcus mutans in Preprimary Children

  2023cited by this paper
• PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein–Barr Virus Reactivation as Trigger Agents?

  2023cited by this paper
• Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.

  2023cited by this paper
• Functional effects of human milk oligosaccharides (HMOs)

  2023cited by this paper
• Emerging issues in probiotic safety: 2023 perspectives

  2023cited by this paper
• T helper 17 (Th17) cell responses to the gut microbiota in human diseases.

  2023cited by this paper
• Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis

  2023cited by this paper
• Influence of the Mediterranean Diet on Healthy Aging

  2023cited by this paper
• Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids

  2023cited by this paper
• Dietary Inflammatory Potential in Pediatric Diseases: A Narrative Review

  2023cited by this paper
• Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome

  2023cited by this paper
• DSS-induced colitis activates the kynurenine pathway in serum and brain by affecting IDO-1 and gut microbiota

  2023cited by this paper
• The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders

  2022cited by this paper
• Obsessive-Compulsive Disorder in PANS/PANDAS in Children: In Search of a Qualified Treatment—A Systematic Review and Metanalysis

  2022cited by this paper
• Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

  2022cited by this paper
• [Parkinson's disease].

  2022cited by this paper
• S3353 Improvement in Paediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Syndrome Following Treatment With a Combination of Antibiotics and Fecal Microbiome Transplantation (FMT)

  2022cited by this paper
• The gut microbiota is important for the maintenance of blood–cerebrospinal fluid barrier integrity

  2022cited by this paper
• The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

  2022cited by this paper
• Protective Effects of Ursodeoxycholic Acid Against Oxidative Stress and Neuroinflammation Through Mitogen-Activated Protein Kinases Pathway in MPTP-Induced Parkinson Disease

  2022cited by this paper
• Therapeutic plasma exchange in adolescent and adult patients with autoimmune neuropsychiatric disorders associated with streptococcal infections

  2022cited by this paper
• Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus—Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits

  2022cited by this paper
• The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer’s Disease

  2022cited by this paper
• Mental health and periodontal and peri‐implant diseases

  2022cited by this paper
• Unveiling the gut-brain axis: structural and functional analogies between the gut and the choroid plexus vascular and immune barriers

  2022cited by this paper
• ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease

  2022cited by this paper
• Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms

  2022cited by this paper
• Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models

  2022cited by this paper
• Microbiota in health and diseases

  2022cited by this paper
• Fermented Foods, Health and the Gut Microbiome

  2022cited by this paper
• Chronic Stress and Depression in Periodontitis and Peri-Implantitis: A Narrative Review on Neurobiological, Neurobehavioral and Immune–Microbiome Interplays and Clinical Management Implications

  2022cited by this paper
• Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia

  2022cited by this paper
• The metabolism-modulating activity of IL-17 signaling in health and disease

  2021cited by this paper
• Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis

  2021cited by this paper
• Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease

  2021cited by this paper
• SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome

  2021cited by this paper
• The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics

  2021cited by this paper
• Obsessive-Compulsive Disorders and Functional Urinary Disorders: A Fortuitous Association?

  2021cited by this paper
• Anti-inflammatory, antibacterial and immunomodulatory treatment in children with symptoms corresponding to the research condition PANS (Pediatric Acute-onset Neuropsychiatric Syndrome): A systematic review

  2021cited by this paper
• Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells.

  2021cited by this paper
• Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease

  2021cited by this paper
• The Impact of the COVID-19 Epidemic During the Lockdown on Children With the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANDAS/PANS): The Importance of Environmental Factors on Clinical Conditions

  2021cited by this paper
• Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with Bifidobacterium dentium

  2021cited by this paper
• Postbiotics — when simplification fails to clarify

  2021cited by this paper
• Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study

  2021cited by this paper
• The AhR ligand 2, 2'-aminophenyl indole (2AI) regulates microglia homeostasis and reduces pro-inflammatory signaling.

  2021cited by this paper
• Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

  2021cited by this paper
• Identification of a choroid plexus vascular barrier closing during intestinal inflammation

  2021cited by this paper
• Invasive Infections Associated with the Use of Probiotics in Children: A Systematic Review

  2021cited by this paper
• Diagnostic Approach to Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS): A Narrative Review of Literature Data

  2021cited by this paper
• Activation

  2021cited by this paper
• Human milk oligosaccharides and infant gut microbiota: Molecular structures, utilization strategies and immune function.

  2021cited by this paper
• A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

  2021cited by this paper
• Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans: relevance for symptoms of anxiety and depression.

  2020cited by this paper

• No citing papers are available for this paper.