Effect of nutritional supplements on gut microbiome in individuals with neurodevelopmental disorders: a systematic review and narrative synthesis

Background: Neurodevelopmental disorders (NDDs) encompass a range of disruptive conditions with varying prevalence rates and multiple contributing factors. Recent studies have suggested a potential connection between NDDs and the gut-brain axis. Furthermore, there is evidence indicating that nutritional supplements might have an impact on gastrointestinal (GI) and behavioral symptoms. This study aimed to explore the effects of nutritional supplements on the gut microbiota and behavioral symptoms in individuals with NDDs. Methods: A systematic search of databases such as PubMed, Scopus, Web of Science, Embase, and APA PsycINFO was conducted, utilizing relevant keywords until February 2025. In addition, the search for gray literature was carried out on Google Scholar and ProQuest. The risk of bias was assessed using the ROBINS-I tool for non-randomized studies and the RoB-1 tool for randomized controlled trials. Due to the heterogeneity of the studies, a Synthesis without Meta-analysis (SWIM) approach was employed. Results: The overall findings from the studies indicated positive effects of supplementation in reducing the Gastrointestinal Severity Index (GIS) score and alleviating GI symptoms. Supplementation with probiotics and vitamins increased good microbiomes and decreased bad microbiomes among individuals with autism spectrum disorder (ASD). Moreover, the Firmicutes to Bacteroidetes ratio exhibited significant changes after supplementation. Additionally, improvements were observed in various assessment scores, including ATEC, ABC, CARS, and PGI-2. Conclusions: Nutritional supplementation in individuals with NDDs can have a positive influence by modulating the microbiome, reducing dysbiosis, and enhancing gut barrier integrity. Shifting in the F/R ratio can be considered as the reason for improving gastrointestinal and behavioral symptoms by influencing neurotransmitter activity and neuroinflammation. Targeting the gut-brain axis with interventions that focus on gut microbiota offers a promising adjunct therapy for the management of NDD. Registration of the review protocol: PROSPERO registration no. CRD42023460449.