The role of the gut mycobiota in neurodevelopmental disorders: a multikingdom disruption of the gut-brain axis

Research on the gut-brain axis in neurodevelopmental disorders (NDDs) has historically focused on bacteria, overlooking fungal contributions. This review synthesizes emerging evidence to propose that intestinal fungi may actively contribute to NDD pathophysiology through multikingdom interactions, though causality requires validation. We delineate a consistent gut mycobiota dysbiosis signature across autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RTT) characterized by reduced diversity and Candida expansion. Potential mechanisms include compromised intestinal barrier integrity, systemic immune activation via Dectin-1/Syk/CARD9 signaling, and disruption of neuroactive metabolites like short-chain fatty acids. We propose distinct etiological pathways: a “top-down” cascade in RTT, where MeCP2 mutation-induced dysmotility creates a pro-dysbiotic niche, and a “bottom-up” pathway in ASD and ADHD, where bacterial dysbiosis erodes colonization resistance, permitting fungal overgrowth. This “bacteria–fungi–host” framework provides a coherent explanation for gut-brain axis disruptions and opens avenues for biomarker discovery and multikingdom therapeutic interventions.