Abstract
Researches on gut microbiota in autism have mostly focused on children, but the dynamic changes of gut microbiota from weaning to adulthood were still not clear because of the difficulty of diagnosing autism. In this study, autistic-like rats indued by valproate (VPA) were tracked from weaning (end of breastfeeding; four weeks old) to sexual maturation (food; eight weeks old). Autistic-like rats were found to show obvious developmental disorders. During weaning, autistic-like rats only exhibited obvious repetitive stereotyped behaviors, but the autistic-like behaviors were fully apparent upon sexual maturation. Significant differences were observed between the gut microbiota of autistic-like and healthy rats across both age groups. The correlation analysis results revealed that the correlation between behaviors and some microbiota, especially Helicobacter, did not vary with age or diet. The total amount of short-chain fatty acids (SCFAs) decreased, butyric acid metabolism decreased, and propionic acid metabolism increased in the feces of autistic-like rats. The correlation between autistic-like behaviors and the butyric acid and propionic acid levels did not vary with diet or age. Inositol phosphate metabolism, amino acid metabolism, and lipopolysaccharide biosynthesis were significantly associated with autistic-like behaviors. Our results showed that although the microbiota and SCFAs related to autism were affected by age and diet, some remained consistent irrespective of age and diet, and they could be considered two of the factors related to autistic-like behaviors development.
Highlights
Autism spectrum disorder (ASD) has been recognized as a broad spectrum of neurodevelopmental disorders frequently occurring in infants and young children
We found that the gut microbiota composition and short-chain fatty acids (SCFAs) levels differ during weaning and sexual maturation between autistic-like and healthy rats
We investigated the changes in the gut microbiota of autistic-like rats from weaning to sexual maturation
Summary
Autism spectrum disorder (ASD) has been recognized as a broad spectrum of neurodevelopmental disorders frequently occurring in infants and young children. It is characterized by impaired social communication (both verbal and non-verbal) and repetitive stereotyped behavior, often accompanied by intellectual disability, epilepsy, or hyperactivity, as well as other clinical symptoms. ASD onset usually occurs before four years of age (Lord et al, 2018). Genetic factors alone cannot fully explain the rapidly increasing incidence of ASD. As such, increasing attention is being paid to the role of non-genetic factors in the pathogenesis of ASD, such as abnormalities in immune regulation, neurotransmitters or signal transmission, and environmental risk factors (Masi et al, 2017)
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