Clinical, immunological and metabolic features and gut-brain axis markers in children with autism spectrum disorder and TORCH-associated central nervous system involvement.
TL;DR
In this cohort, ASD with clinical evidence of TORCH-associated central nervous system involvement was associated with greater clinical severity and higher serum inflammatory, metabolic, neuronal-injury, fecal-zonulin, and structural MRI measures than ASD without such evidence.
Abstract
Background
Autism spectrum disorders (ASD) have heterogeneous etiologies, with TORCH infections potentially contributing to neurodevelopmental disruption through central nervous system injury and gut-brain axis dysfunction.
Methods
A prospective comparative study enrolled 280 children aged 3-10 years with ASD: 112 with TORCH-associated central nervous system (CNS) involvement (main group) and 168 with idiopathic ASD (comparison group), alongside 25 healthy controls. Assessments included clinical/neurological features, autism severity, gastrointestinal symptoms, pro-inflammatory cytokines, metabolic markers, neuron-specific enolase (NSE), fecal zonulin, and brain MRI. TORCH pathogens were detected by PCR from saliva samples.
Results
TORCH-associated ASD exhibited a more severe phenotype with greater frequencies of delayed speech, cognitive impairment, sleep disturbance, hyperactivity, emotional-behavioral dysregulation, epileptiform manifestations, and gastrointestinal symptoms. Severe ASD was significantly more common in the TORCH group. Laboratory analyses revealed significantly elevated interleukin-1β, interleukin-8, tumor necrosis factor alpha, homocysteine, ammonia, uric acid, NSE, and fecal zonulin, with reduced folate. Fecal zonulin was positively correlated with inflammatory markers and neuron-specific enolase. MRI more frequently demonstrated periventricular gliosis, ventriculomegaly, subependymal abnormalities, and diffuse residual organic changes.
Conclusions
In this cohort, ASD with clinical evidence of TORCH-associated CNS involvement was associated with greater clinical severity and higher serum inflammatory, metabolic, neuronal-injury, fecal-zonulin, and structural MRI measures than ASD without such evidence. The cross-sectional design and limitations of salivary PCR preclude causal attribution to TORCH infection.