Disrupted gut harmony in attention-deficit/hyperactivity disorder: Dysbiosis and decreased short-chain fatty acids

Abstract

Background: Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder with complex genetic and environmental underpinnings. Emerging evidence suggests a significant role of gut microbiota in ADHD pathophysiology. This study investigates variations in gut microbiota composition and Short-Chain Fatty Acid (SCFA) profiles between children and adolescents with ADHD and healthy controls. Methods: The study included 42 ADHD patients and 31 healthy controls, aged 6–18 years. Fecal samples were analyzed for microbial composition using 16S rRNA gene sequencing and for SCFA profiles through gas chromatography-mass spectrometry (GC-MS). The study assessed both α and β diversity of gut microbiota and quantified various SCFAs to compare between the groups. Results: ADHD subjects demonstrated significantly reduced gut microbiota diversity, as indicated by lower α-diversity indices (Shannon index, Observed species, Faith PD index) and a trend towards significance in β-diversity (Weighted UniFrac). Notably, the ADHD group exhibited significantly lower levels of key SCFAs, including acetic, propionic, isobutyric, isovaleric, and valeric acids, highlighting a distinct microbial and metabolic profile in these individuals. Conclusion: This study uncovers significant alterations in gut microbiota and SCFA profiles in children with ADHD, compared to healthy controls. The observed changes in SCFAs, known for their associations with other behavioral and neurologic pathologies, and for their role in neural signaling. These findings offer a metabolite fingerprint that could potentially lead to novel diagnostic and treatment approaches for ADHD, emphasizing the importance of gut microbiota in the disorder’s pathogenesis and management.

Keywords

• Attention deficit hyperactivity disorder
• Dysbiosis
• Microbiota-gut-brain axis
• Microbiome
• Short-chain fatty acids
• Akkermansia