The differential diagnosis between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) is often challenging and detrimental to early and timely treatment. Co-current and overlapping symptoms contribute to erode differential diagnostic accuracy, based mainly on clinical assessment supported by standardized instruments and reports from parents and teachers. The microbiota was recently considered a valuable resource in the search for biological markers in neurodevelopmental disorders.

Our objective was to examine the published literature in order to clarify the role of the microbiome as a possible differential biomarker between ASD and ADHD.

Five hundred and sixteen articles were reviewed in order to contextualize the role of Gut- Brain Axis in neurodevelopment and neurodevelopmental disorders, the microbiome as a biomarker and ultimately to unravel microbiome abnormalities reported in patients diagnosed with ASD and/or ADHD.

Although gut microbiome appears to be involved in the pathogenesis of ASD with several reports identifying changes in gut populations and functions, a “microbial signature” is still not reached. In ADHD patients, research confirms that the composition and predicted functions of gut microbiome are also altered, but identically controversial results were found.

Future studies are needed to confirm the relationship between the composition and function of the microbiome and the occurrence or presentation of each of the disorders. A specific signature of the microbiota could then constitute itself as a differential biomarker in ASD and ADHD.