The Oral-Gut-Brain Axis in Pediatric Populations: The Implications of Oral Dysbiosis for Systemic Inflammation and Neuroinflammation.

Background

The oral microbiome plays a fundamental role in maintaining local and systemic health during childhood, a developmental period characterized by dynamic microbial, immune, and neuroendocrine maturation. Increasing evidence suggests that oral dysbiosis may influence gut microbiota composition, systemic inflammation, and neuroinflammatory pathways through the oral-gut-brain axis. Aim: This narrative review aimed to summarize and critically evaluate current evidence regarding the relationship between oral dysbiosis, gut microbial alterations, systemic inflammation, and neurodevelopmental processes in pediatric populations.

Methods

A search of the literature was conducted using PubMed, Scopus, and Web of Science, including studies published between January 2016 and April 2026. Eligible studies included randomized controlled trials, observational studies, and reviews investigating at least one component of the oral-gut-brain axis in children or adolescents.

Results

Current evidence supports a biological interaction between oral and gut microbiota through microbial translocation and immune-mediated mechanisms. Oral dysbiosis may contribute to gut microbial imbalance, intestinal barrier dysfunction, and systemic low-grade inflammation. Altered gut microbiota has been associated with neuroinflammatory signaling, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and adverse neurodevelopmental outcomes. Furthermore, pediatric randomized controlled trials suggest that probiotics and synbiotics can modulate oral and gut microbial composition, improve selected inflammatory and immune biomarkers, and reduce salivary cortisol levels.

Conclusions

The oral-gut-brain axis represents a promising framework for understanding the systemic consequences of oral dysbiosis during childhood. However, direct evidence integrating oral, intestinal, immunological, and neurodevelopmental outcomes remains limited, highlighting the need for longitudinal and multidisciplinary pediatric studies.