The autistic-like behaviors development during weaning and sexual maturation in VPA-induced autistic-like rats is accompanied by gut microbiota dysbiosis

Qingmin Kong; Peijun Tian; Jianxin Zhao; Hao Zhang; Gang Wang; Wei Chen

doi:10.7717/peerj.11103

The autistic-like behaviors development during weaning and sexual maturation in VPA-induced autistic-like rats is accompanied by gut microbiota dysbiosis

PeerJ. 2021 May 3:9:e11103. doi: 10.7717/peerj.11103. eCollection 2021.

Authors

Qingmin Kong^{1

2}, Peijun Tian^{1

2}, Jianxin Zhao^{1

2

3

4}, Hao Zhang^{1

2

4

5

6}, Gang Wang^{1

2

3

4}, Wei Chen^{1

2

5

7}

Affiliations

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
² School of Food Science and Technology, Jiangnan University, Wuxi, China.
³ International Joint Research Laboratory for Probiotics & Gut Health, Jiangnan University, Wuxi, P. R. China.
⁴ (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Wuxi, P. R. China.
⁵ National Engineering Center of Functional Food, Jiangnan university, Wuxi, China.
⁶ Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi, China.
⁷ Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.

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.

Keywords: Autism spectrum disorder; Behavioristics; Gutmicrobiota; Sexual maturation; Weaning.

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (No. 31972052, 31671839, 31820103010), the National Natural Science Foundation of China Key Program (No. 31530056), the Fundamental Research Funds for the Central Universities (JUSRP22006, JUSRP51501), the National First-class Discipline Program of Food Science and Technology (JUFSTR20180102) and the collaborative innovation center of food safety and quality control in Jiangsu Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.