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

Abstract

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.

• Authors: Jie Li, Huidi Wang, Wei Qing, Feitong Liu, Nianyi Zeng, Fan Wu, Yiya Shi, Xuxuan Gao, Ming Cheng, Hailong Li, Wei Shen, Fangguo Meng, Yan He, Muxuan Chen, Zhuang Li, Hongwei Zhou, Qian Wang
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 105 Pg. 15-26 (10 2022) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 35714916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Valproic Acid

Topics

• Animals
• Autism Spectrum Disorder
• Autistic Disorder
• Dysbiosis
• Gastrointestinal Diseases
• Gastrointestinal Microbiome
• Intestines
• Mice
• Valproic Acid