Clinical, immunological and metabolic features and gut-brain axis markers in children with autism spectrum disorder and TORCH-associated central nervous system involvement.

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.