Harnessing the microbiota-gut–brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies

Pediatric neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Rett syndrome (RTT), Tourette syndrome (TS), Down syndrome (DS), Fragile X syndrome (FXS), Prader–Willi syndrome (PWS), fetal alcohol spectrum disorder (FASD), pediatric epilepsy, congenital Zika syndrome (CZS), Wilson’s disease (WD), and cerebral palsy (CP), are associated with long-term impairments and high societal burden. Emerging evidence implicates the microbiota–gut–brain axis (MGBA) in early neurodevelopment with factors, such as maternal microbiota, birth mode, antibiotics, and infant diet shaping microbial colonization and influencing developmental outcomes. This review aims to synthesize current translational evidence from animal and human studies to address the following research questions: (1) How do disruptions in the MGBA contribute to the pathophysiology of pediatric neurodevelopmental disorders? (2) What microbiome alterations are consistently associated with these conditions? and (3) What ethical and safety considerations should be addressed in implementing early-life microbiome-based interventions? We also assess emerging microbiota-based interventions, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and traditional therapies, and their potential to modulate disease outcomes. The MGBA presents a promising, yet currently preliminary, target for early intervention in pediatric neurodevelopmental disorders. There is emerging evidence that therapies targeting the microbiota could have an effect on neurodevelopment and outcomes of health and disease; however, most of the findings are in the initial stages, and the evidence is still inconsistent. Therefore, the findings must be translated into mechanisms of action over extended periods with longitudinal multi-omic studies to identify possible intervention windows, optimize personalized therapies, and evaluate the safety and efficacy of interventions targeting the microbiome. Till that point, these microbiota-targeted approaches should be approached cautiously and treated as experimental in the realm of pediatric interventions, given the present-day state of evidence. The microbiota–gut–brain axis plays a key role in pediatric neurodevelopment. Disruption in the microbiota–gut–brain axis is associated with disorders like autism, attention deficit hyperactivity disorder, Rett syndrome, Tourette syndrome, and Down syndrome. Microbiome-based therapies are promising but are still at preliminary stages. Knowledge gaps persist in issues of causality, long-term safety, and standardization of interventions. Future studies will require large, longitudinal, multi-omics research to ensure safety within the pediatric population.