Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

The effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valp...

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Main Authors: Jingjing Fang, Ruixuan Geng, Seong-Gook Kang, Kunlun Huang, Tao Tong
Format: Article
Language:English
Published: Tsinghua University Press 2024-09-01
Series:Food Science and Human Wellness
Subjects:
Online Access:https://www.sciopen.com/article/10.26599/FSHW.2022.9250234
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author Jingjing Fang
Ruixuan Geng
Seong-Gook Kang
Kunlun Huang
Tao Tong
author_facet Jingjing Fang
Ruixuan Geng
Seong-Gook Kang
Kunlun Huang
Tao Tong
author_sort Jingjing Fang
collection DOAJ
description The effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valproic acid (VPA)-induced mouse model of ASD. Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice. The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition. The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex (PFC) induced by VPA exposure. RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease, neuroactive ligand-receptor interaction, oxidative phosphorylation, and mitogen activated protein kinase signaling pathway. Overall, dietary Pro supplementation may be a promising intervention strategy for ASD.
format Article
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institution Kabale University
issn 2097-0765
2213-4530
language English
publishDate 2024-09-01
publisher Tsinghua University Press
record_format Article
series Food Science and Human Wellness
spelling doaj-art-4060f29a52c745c39553268ef8b91a862025-01-10T06:56:56ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-09-011352889290510.26599/FSHW.2022.9250234Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorderJingjing Fang0Ruixuan Geng1Seong-Gook Kang2Kunlun Huang3Tao Tong4Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaDepartment of Food Engineering and Solar Salt Research Center, Mokpo National University, Muangun 58554, KoreaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaThe effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valproic acid (VPA)-induced mouse model of ASD. Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice. The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition. The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex (PFC) induced by VPA exposure. RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease, neuroactive ligand-receptor interaction, oxidative phosphorylation, and mitogen activated protein kinase signaling pathway. Overall, dietary Pro supplementation may be a promising intervention strategy for ASD.https://www.sciopen.com/article/10.26599/FSHW.2022.9250234l-prolineautism spectrum disordergut microbiotaprefrontal cortexbehavior
spellingShingle Jingjing Fang
Ruixuan Geng
Seong-Gook Kang
Kunlun Huang
Tao Tong
Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
Food Science and Human Wellness
l-proline
autism spectrum disorder
gut microbiota
prefrontal cortex
behavior
title Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
title_full Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
title_fullStr Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
title_full_unstemmed Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
title_short Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder
title_sort dietary l proline supplementation ameliorates autism like behaviors and modulates gut microbiota in the valproic acid induced mouse model of autism spectrum disorder
topic l-proline
autism spectrum disorder
gut microbiota
prefrontal cortex
behavior
url https://www.sciopen.com/article/10.26599/FSHW.2022.9250234
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AT seonggookkang dietarylprolinesupplementationamelioratesautismlikebehaviorsandmodulatesgutmicrobiotainthevalproicacidinducedmousemodelofautismspectrumdisorder
AT kunlunhuang dietarylprolinesupplementationamelioratesautismlikebehaviorsandmodulatesgutmicrobiotainthevalproicacidinducedmousemodelofautismspectrumdisorder
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