Congenitally underdeveloped intestine drives autism-related gut microbiota and behavior

•The intestine of VPA-exposed mice is underdeveloped with excess oxidative stress.•The underdeveloped intestine of VPA-exposed mice influences the colonization of gut microbiota.•Supplementation of SOD during early life restores the autism-related gut microbiota.•SOD supplementation before weaning o...

Full description

Saved in:
Bibliographic Details
Published in:Brain, behavior, and immunity behavior, and immunity, 2022-10, Vol.105, p.15-26
Main Authors: Li, Jie, Wang, Huidi, Qing, Wei, Liu, Feitong, Zeng, Nianyi, Wu, Fan, Shi, Yiya, Gao, Xuxuan, Cheng, Ming, Li, Hailong, Shen, Wei, Meng, Fangguo, He, Yan, Chen, Muxuan, Li, Zhuang, Zhou, Hongwei, Wang, Qian
Format: Article
Language:English
Subjects:
Autism spectrum disorder
Behavior
Gut microbiota
Oxidative stress
Superoxide dismutase
Underdeveloped intestine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•The intestine of VPA-exposed mice is underdeveloped with excess oxidative stress.•The underdeveloped intestine of VPA-exposed mice influences the colonization of gut microbiota.•Supplementation of SOD during early life restores the autism-related gut microbiota.•SOD supplementation before weaning or during juvenile ameliorates autistic behavior. 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.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2022.06.006