Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats

Introduction: The microbiota–gut–brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbi...

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Main Authors: Jiu-Gen Zhong, Wan-Ting Lan, Yan-Qing Feng, Yin-Hua Li, Ying-Ying Shen, Jia-Heng Gong, Zhi Zou, Xiaohui Hou
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2023.1077821/full
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author Jiu-Gen Zhong
Jiu-Gen Zhong
Wan-Ting Lan
Yan-Qing Feng
Yin-Hua Li
Yin-Hua Li
Ying-Ying Shen
Jia-Heng Gong
Zhi Zou
Xiaohui Hou
Xiaohui Hou
author_facet Jiu-Gen Zhong
Jiu-Gen Zhong
Wan-Ting Lan
Yan-Qing Feng
Yin-Hua Li
Yin-Hua Li
Ying-Ying Shen
Jia-Heng Gong
Zhi Zou
Xiaohui Hou
Xiaohui Hou
author_sort Jiu-Gen Zhong
collection DOAJ
description Introduction: The microbiota–gut–brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats.Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography–mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC).Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids.Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota–gut–brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.
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spelling doaj.art-50dd5e2b8d434bf1b56c18eff3cf28e62023-03-22T05:17:07ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-03-011410.3389/fphys.2023.10778211077821Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model ratsJiu-Gen Zhong0Jiu-Gen Zhong1Wan-Ting Lan2Yan-Qing Feng3Yin-Hua Li4Yin-Hua Li5Ying-Ying Shen6Jia-Heng Gong7Zhi Zou8Xiaohui Hou9Xiaohui Hou10School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Kinesiology, Shanghai University of Sport, Shanghai, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Kinesiology, Shanghai University of Sport, Shanghai, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, ChinaSchool of Kinesiology, Shanghai University of Sport, Shanghai, ChinaIntroduction: The microbiota–gut–brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats.Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography–mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC).Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids.Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota–gut–brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.https://www.frontiersin.org/articles/10.3389/fphys.2023.1077821/fullautism spectrum disordermicrobiotashort-chain fatty acidsneurotransmittervalproic acid
spellingShingle Jiu-Gen Zhong
Jiu-Gen Zhong
Wan-Ting Lan
Yan-Qing Feng
Yin-Hua Li
Yin-Hua Li
Ying-Ying Shen
Jia-Heng Gong
Zhi Zou
Xiaohui Hou
Xiaohui Hou
Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
Frontiers in Physiology
autism spectrum disorder
microbiota
short-chain fatty acids
neurotransmitter
valproic acid
title Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
title_full Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
title_fullStr Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
title_full_unstemmed Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
title_short Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats
title_sort associations between dysbiosis gut microbiota and changes of neurotransmitters and short chain fatty acids in valproic acid model rats
topic autism spectrum disorder
microbiota
short-chain fatty acids
neurotransmitter
valproic acid
url https://www.frontiersin.org/articles/10.3389/fphys.2023.1077821/full
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