Genotype-specific digital twins for arrhythmia ablation targeting in arrhythmogenic right ventricular cardiomyopathy.

Neurodevelopmental disorders (NDDs) constitute a heterogeneous group of conditions characterized by impairments in motor, cognitive, behavioral, and social functioning, with onset typically occurring during early childhood. NDDs are highly prevalent in pediatric populations and encompass a broad range of conditions, including epilepsy, Down syndrome (DS), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), Cerebral Palsy (CP), Fetal Alcohol Spectrum Disorder (FASD), Fragile X syndrome (FXS), Tourette syndrome (TS), Rett syndrome (RTT), Prader-Willi syndrome (PWS), Congenital Zika Syndrome (CZS), and Wilson’s Disease (WD). These disorders affect an estimated 10–15% of children worldwide and represent a leading cause of lifelong disability and societal burden (; ). Historically, the classification of NDDs has progressively shifted from a functional symptomatic-based framework to a more etiological paradigm that emphasizes underlying biologic mechanisms rather than behavioral phenotypes (). A unifying etiological framework of NDDS has gradually emerged, proposing that these disorders exist along a continuum rooted in shared biological mechanisms, (), based upon a common cornerstone, has gradually emerged. As genetic and central nervous system–centric models could not fully account for the complexity and heterogeneity observed across clinical phenotypes, increasing attention has been drawn to the role of environmental and systemic factors in shaping neurodevelopmental outcomes. Among these, the gut microbiota has emerged as a critical regulator of neurodevelopment (; ; ). The human gastrointestinal tract harbors a vast and dynamic community of microorganisms, collectively referred to as the microbiome, which plays a fundamental role in host physiology. The microbiota is involved in a wide range of processes, including nutrient metabolism, immune system development, and the synthesis of bioactive compounds capable of influencing brain function (). Dysbiosis, defined as an imbalance in the composition and function of the gut microbiota, has been increasingly implicated in the pathogenesis of neurodevelopmental disorders. This imbalance may involve reduced microbial diversity, loss of beneficial commensal species, or overgrowth of potentially pathogenic organisms. Disruptions of this finely tuned system during this critical developmental window may exert disproportionate effects on neural development, with lasting consequences, contributing to the emergence of NDDs. Consistent with this hypothesis, alterations in gut microbiota composition have been identified across a range of neurodevelopmental disorders (; ; ; ). Clinical studies have similarly linked early-life microbiota perturbations—such as those induced by antibiotic exposure—to an increased risk of NDDs (). Accumulating evidence supports a potential causal relationship. Longitudinal data, including a large Swedish cohort study following 16,440 children over two decades, support an association between early-life microbial perturbations and later NDD risk (). Complementary mechanistic insights are provided by preclinical studies demonstrating that transplantation of gut microbiota from individuals with autism spectrum disorder into germ-free mice can recapitulate behavioral and neurobiological features of the condition ().