Mistura probiótica derivada de kefir em crianças com transtorno do espectro autista: estudo randomizado, duplo-cego e controlado por placebo

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interactions and restricted patterns of behavior. Recent evidence has identified the gut microbiota as a modulator of neurobehavioral and inflammatory aspects related to ASD, fostering interest in probiotic and symbiotic interventions. This randomized, double-blind, placebo-controlled study evaluated the effects of a kefirderived probiotic formulation (K11) and a version enriched with vitamins, amino acids, and minerals (K11-TMAX) in children with ASD. A total of 182 children aged 3 to 11 years were assigned to three groups: placebo, K11, and K11-TMAX, with assessments conducted at baseline, 45, and 90 days. The primary endpoint was the Adaptive Behavior Composite (ABC) score of the Vineland Adaptive Behavior Scales – Third Edition (Vineland-3). Secondary outcomes included other Vineland-3 subdomains, scores from the Autism Diagnostic Observation Schedule – Second Edition (ADOS-2), and the Childhood Autism Rating Scale (CARS), as well as inflammatory and metabolic biomarkers. After 90 days, the K11 and K11-TMAX groups showed significant improvements (p < 0.05) in ABC scores, as well as in the communication, daily living skills, motor skills, and internalizing/externalizing behavior subdomains. The K11 group also showed a significant improvement in socialization. ADOS-2 assessments demonstrated statistically significant reductions in core ASD symptoms in both intervention groups, while CARS scores, as rated by teachers, revealed a reduction in clinical severity within the school context. Biochemical analyses revealed significantly reduced serum insulin and C-reactive protein levels in the K11 and K11-TMAX groups, along with a significant reduction in fecal calprotectin levels in the K11-TMAX group. There was a significant reduction in serum cortisol levels in the symbiotic intervention groups at day 45, suggesting an improvement in the systemic inflammatory profile. Microbiota analysis indicated a significant increase in Lactobacillus counts and a reduction in Escherichia coli in the probiotic groups. Such changes are associated with the restoration of eubiosis and the potential increase in the production of neuroactive and anti-inflammatory metabolites. The results indicate that K11 and K11-TMAX are safe and capable of producing clinical, metabolic, and microbiological benefits in children with ASD, aligning with the gut–brain axis hypothesis and representing promising adjuvant interventions in the multidimensional management of the condition.