Abstract
<jats:p>Objective: To systematically review the literature on the association between the oral microbiota and the gut-brain axis in the context of Autism Spectrum Disorder (ASD), investigating whether alterations in the oral microbial ecosystem reflect systemic processes related to the disorder. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Electronic searches were performed in Embase, PubMed, Scopus, and Web of Science using descriptors related to oral microbiota, ASD, and the gut-brain axis. Human studies published between 2015 and 2025 that evaluated the oral microbiota (saliva, dental plaque, or oral swab) and its association with ASD-related outcomes were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists, and study selection was managed using Rayyan software. Twelve studies met the eligibility criteria and were included in the qualitative synthesis. Results: The included studies consistently demonstrated alterations in the composition, diversity, and richness of the oral microbiota in individuals with ASD compared with healthy controls, indicating a dysbiotic microbial profile. The predominant bacterial phyla identified were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteriota, and Fusobacteriota. These microbial alterations were associated with clinical, behavioral, inflammatory, and metabolic outcomes. Furthermore, studies simultaneously evaluating the oral and gut microbiota suggested systemic interactions, with shared dysbiotic profiles supporting the role of the oral cavity as a potential source of biomarkers and as a component of the oral-gut-brain axis. Conclusions: The oral microbiota appears to be an integral component of the gut-brain axis in ASD and should not be investigated in isolation. Current evidence indicates that oral microbial dysbiosis is associated with the clinical manifestations and pathophysiological mechanisms of ASD. Although further studies involving larger populations and standardized methodologies are required, the available findings support the oral microbiota as a promising target for the development of diagnostic biomarkers and complementary therapeutic strategies for personalized ASD care.</jats:p>