Abstract
BACKGROUND: Emerging evidence suggests a link between the oral microbiome and autism spectrum disorder (ASD), a neurodevelopmental condition characterised by social and behavioural impairments. The vast microbial reservoirs in the gut complement those of the oral cavity, suggesting a potential oral-gut-brain axis that may influence ASD and perhaps other neurological diseases, such as Parkinson's syndrome and Alzheimer's disease. For the first time, this systematic review synthesises the current knowledge of oral microbiome composition, diversity, and functionality in ASD and its potential diagnostic and therapeutic implications. METHODS: A comprehensive literature search was conducted using Medline (PubMed), Embase, Scopus, and Google Scholar for peer-reviewed case-control and cross-sectional studies published between January 2000 and January 2025. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: Nine studies (n = 8533; 2536 ASD and 5937 controls) met the inclusion criteria. The overall findings on microbial diversity were inconsistent; some studies reported alterations in ASD, while others found no significant differences. Functional profiling revealed enrichment of pathways involved in dopamine and GABA degradation, as well as disruptions in lysine metabolism, suggesting possible links to neurotransmitter imbalances in ASD. Although external factors such as selective eating, oral hygiene, and cognitive function were proposed to influence microbial profiles, statistical evidence supporting these associations was lacking. Moreover, no consistent link was found between oral microbiota features and core ASD symptoms like repetitive behaviours or communication deficits. CONCLUSION: This review highlights subtle yet potentially significant alterations in the oral microbiome of individuals with ASD, particularly in metabolic pathways that affect neurotransmitters. While direct associations with clinical symptoms remain unsubstantiated, the findings emphasise the importance of future multi-omics and longitudinal studies to clarify the oral microbiome's role in ASD pathophysiology and to explore its potential in personalised therapeutic strategies.