Congenitally underdeveloped intestine drives autism-related gut microbiota and behavior.

Scientists studied mice with autism-like traits and found they had underdeveloped intestines from birth, which led to an imbalanced gut microbiome (the bacteria in the gut). When researchers gave these mice a treatment to reduce harmful chemicals in the gut, both the gut bacteria and autism-like behaviors improved. This suggests that gut problems might start very early and could contribute to autism symptoms.

This preclinical study investigated the relationship between intestinal development and autism-related gut microbiota using a valproic acid (VPA)-induced autism mouse model. Researchers found that VPA-exposed mice had congenitally immature intestines with increased oxidative stress and inflammation. While gut microbiota was initially similar between VPA-exposed and control mice at birth, significant differences emerged by postnatal days 7 and 21. Importantly, oral administration of superoxide dismutase (SOD) to reduce intestinal oxidative stress successfully restored normal gut microbiota composition and improved autism-related behaviors.

The findings suggest that underdeveloped intestinal function may be an early driver of autism-associated gut dysbiosis through oxidative stress mechanisms, potentially influencing neurodevelopment.

Results suggest early intestinal dysfunction and oxidative stress may contribute to autism-related gut dysbiosis and behavioral symptoms. This supports early gut health interventions and antioxidant approaches, though human studies are needed to confirm clinical relevance and safety.

This is an animal study using chemically-induced autism model, which may not fully represent human autism. Sample sizes and statistical details are not reported. The generalizability to human autism and clinical translation remain unclear.

Autism spectrum disorder (ASD) is a neurological and developmental disorder accompanied by gut dysbiosis and gastrointestinal symptoms in most cases. However, the development of the autism-related gut microbiota and its relationship with intestinal dysfunction in ASD remain unclear. Using a valproic acid (VPA)-induced ASD mouse model, we showed a congenitally immature intestine of VPA-exposed mice accompanied by prominent oxidative stress and inflammation. Of note, the gut microbiota composition of VPA-exposed mice resembled that of control mice within 24 h after birth; however, their gut microbiota compositions differed on postnatal days 7 and 21.

Oral administration of superoxide dismutase (SOD) to attenuate intestinal oxidative stress either before weaning or during juvenile restored the autism-associated gut microbiota, leading to the amelioration of autism-related behaviors. These findings collectively suggest the congenitally underdeveloped intestine as an early driving force shaping the autism-associated gut microbiota and host neurodevelopment through enhancing oxidative stress.