Potential gut–brain axis-targeted therapies for autism spectrum disorder in children: opportunities and challenges

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Abstract
Background Autism spectrum disorder (ASD) lacks definitive treatment, but recent research has highlighted the potential of gut‒brain axis-targeted therapies for managing ASD symptoms in children. This review evaluated the effects of microbiota transplantation (MT), probiotics, dietary interventions, and nutritional supplements on ASD symptoms in children. Data sources A systematic review was conducted via PubMed/MEDLINE, Scopus, and Web of Science to identify studies published up to June 2024. The inclusion criteria consisted of peer-reviewed articles encompassing both observational studies and interventional trials, and studies specifically targeted symptoms of ASD and included patients under the age of 18, with a minimum sample size of 20 participants. Results Of the 3424 identified studies, 31 met the inclusion criteria. MT emerged as the most consistently effective intervention, showing improvements across multiple symptom domains, including behavior and social interaction, particularly for individuals with severe gastrointestinal (GI) issues. Probiotics have reported strain-specific efficacy, with some studies reporting behavioral improvements, but the results have been inconsistent. Dietary interventions, such as gluten-free casein-free and modified Atkins diets, have shown partial efficacy, particularly for individuals with cooccurring GI symptoms, with adherence challenges and variability in outcomes. Nutritional supplements yielded mixed outcomes, highlighting the need for personalized approaches. Despite promising findings, significant heterogeneity in study protocols and outcome measures underscores the need for standardized methodologies. Future research should prioritize standardization of these protocols. Long-term studies and longitudinal designs can help increase the reliability and practicality. Precision strategies based on individual microbiota compositions and genomics could optimize outcomes. Combined therapies should undergo rigorous evaluation. Reliable markers could improve cost-effectiveness by targeting therapies to responders. Broader research populations, economic evaluations, new technologies and interdisciplinary research will contribute to achieving a broader application and better outcomes. Conclusions This review emphasizes the potential of gut‒brain axis-targeted therapies to improve the quality of life of children with ASD and their families. MT showed the most consistent improvements in managing pediatric ASD symptoms, with probiotics, dietary interventions, and nutritional supplements offering additional, albeit variable benefits. Efforts should be made to standardize the protocols, to conduct long-term studies, and to explore cost-effective solutions to ensure accessibility, particularly in resource-limited settings. Graphical abstract
Funding Information
  • Kyung Hee University (20230895)

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