Microbiota intestinal, metabólitos fecais e biomarcadores salivares em crianças com tea: impactos da terapia multiprofissional sobre o eixo intestino–cérebro

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and restricted, repetitive patterns of behavior. Growing evidence suggests that alterations in the gut microbiota may contribute to its pathophysiology. This study aimed to characterize the gut microbiota of children with ASD and investigate its association with clinical, behavioral, and gestational factors, considering the duration of multidisciplinary therapeutic intervention. This was an observational, cross-sectional, case-control study including children aged 3 to 12 years with and without ASD. The study included 46 children with ASD recruited from the Early Treatment and Stimulation Center of the Federal University of Ceará (Núcleo de Tratamento e Estimulação Precoce – UFC) and 16 neurotypical children. Sociodemographic, gestational, and clinical data were collected using a structured questionnaire, and adaptive behavior was assessed using the Vineland-3. Gut microbiota composition was determined by 16S rRNA gene sequencing (Illumina NextSeq). Fecal metabolites and salivary biomarkers were quantified using HPLC, LC-MS/MS, ELISA, and SIMOA. Among children with ASD, 80.43% were male, 50% presented associated comorbidities, 62.86% had been exposed to gestational stress (p=0.0059), and 42.22% required neonatal hospitalization (p=0.0115). The ASD group showed lower scores across all Vineland-3 domains (p<0.0001). Gut microbiota analysis revealed significant differences in beta diversity between groups (PERMANOVA p=0.002; ANOSIM p=0.001), reduced alpha diversity in the ASD group (Observed richness p=0.024; Chao1 p=0.027; 1/Simpson index p=0.044), and an increased Firmicutes/Bacteroidota ratio (p=0.01). Differential abundance analysis identified enrichment of taxa belonging to the phyla Bacteroidota and Fusobacteriota in the control group, including the genera Bacteroides, Parabacteroides, and Fusobacterium, whereas the ASD group showed enrichment of taxa belonging to the phyla Actinomycetota and Pseudomonadota, particularly the genus Blautia, the family Eggerthellaceae, and the class Gammaproteobacteria. Children with a shorter duration of therapeutic intervention exhibited lower microbial richness and diversity, whereas those with prolonged intervention displayed microbial diversity profiles similar to those of the control group. Metabolic profiling revealed increased GABA (p=0.0041) and tryptophan (p=0.0146) levels in the ASD group. Children with shorter therapeutic intervention showed higher tryptophan levels (p=0.0271), whereas GABA (p=0.0298) and glutamate (p=0.0383) were associated with poorer Communication scores, and GABA (p=0.0309) and serotonin (p=0.0445) were associated with lower Adaptive Behavior Composite (ABC) scores. Children with ASD also exhibited reduced cortisol levels (p=0.0039) and an increased Aβ42/Aβ40 ratio (p=0.0461), suggesting hypothalamic-pituitary adrenal (HPA) axis dysfunction and possible neuroinflammation. Furthermore, the association between longer multidisciplinary therapeutic intervention and microbial diversity profiles similar to those observed in the control group reinforces the potential of the gut microbiota as a target for future therapeutic strategies in ASD