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粪便移植及治疗可调节肠道细菌,并挽救自闭症啮齿动物模型中的社交障碍及海马脑源性神经营养因子表达。

Fecal Transplant and Treatments Modulate Gut Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.

作者信息

Abuaish Sameera, Al-Otaibi Norah M, Abujamel Turki S, Alzahrani Saleha Ahmad, Alotaibi Sohailah Masoud, AlShawakir Yasser A, Aabed Kawther, El-Ansary Afaf

机构信息

Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.

Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.

出版信息

Brain Sci. 2021 Aug 5;11(8):1038. doi: 10.3390/brainsci11081038.


DOI:10.3390/brainsci11081038
PMID:34439657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8391663/
Abstract

Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal with a concomitant decrease in cluster IV, and exhibited high hippocampal expression compared to controls. Fecal microbiota transplantation or treatment restored the balance of fecal spp. and normalized the level of expression. These findings highlight the involvement of the gut-brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.

摘要

自闭症与胃肠功能障碍和肠道微生物群失调有关,包括不同粪便菌属水平的总体增加。调节肠道微生物群被认为可以改善自闭症症状。在本研究中,我们在自闭症啮齿动物模型中探索了针对微生物群的两种不同干预措施的实施及其对社交行为的影响:不同粪便菌属的水平以及海马体转录水平。通过对幼龄斯普拉格-道利雄性大鼠连续三天口服灌喂丙酸(PPA)来诱导自闭症,而对照组大鼠接受生理盐水灌喂。接受PPA处理的动物被分为三组,分别接受生理盐水、来自健康供体大鼠的粪便移植或[此处原文缺失具体干预措施内容],持续22天,而对照组继续接受生理盐水灌喂。我们发现PPA会减弱动物的社交互动,而这两种干预措施可使其恢复。与对照组相比,接受PPA处理的动物粪便中[此处原文缺失具体菌属名称]的丰度显著增加,同时[此处原文缺失具体菌属名称]第四簇减少,并且海马体[此处原文缺失具体基因名称]表达较高。粪便微生物群移植或[此处原文缺失具体干预措施内容]处理恢复了粪便菌属的平衡,并使[此处原文缺失具体基因名称]表达水平正常化。这些发现突出了肠-脑轴在自闭症病因中的作用,并在自闭症临床前模型中提出了可能的干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/55ce4cae79e8/brainsci-11-01038-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/1e01eb9abb08/brainsci-11-01038-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/a3d9d531f53e/brainsci-11-01038-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/e7eb3fd2abb8/brainsci-11-01038-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/1a37f7aedbb8/brainsci-11-01038-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/55ce4cae79e8/brainsci-11-01038-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/1e01eb9abb08/brainsci-11-01038-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/a3d9d531f53e/brainsci-11-01038-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/e7eb3fd2abb8/brainsci-11-01038-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/1a37f7aedbb8/brainsci-11-01038-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262a/8391663/55ce4cae79e8/brainsci-11-01038-g005.jpg

相似文献

[1]
Fecal Transplant and Treatments Modulate Gut Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.

Brain Sci. 2021-8-5

[2]
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J Mol Neurosci. 2022-2

[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder.

Gut Microbes. 2025-12

[2]
Impact of GABA and nutritional supplements on neurochemical biomarkers in autism: a PPA rodent model study.

Front Mol Neurosci. 2025-3-18

[3]
Fecal microbiota transplants in pediatric autism: opportunities and challenges.

World J Pediatr. 2024-12

[4]
In a rodent model of autism, probiotics decrease gut leakiness in relation to gene expression of GABA receptors: Emphasize how crucial the gut-brain axis.

Transl Neurosci. 2024-10-3

[5]
Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Inflammation. 2025-4

[6]
Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of intervention.

Gut Microbes. 2024

[7]
Effects and microbiota changes following oral lyophilized fecal microbiota transplantation in children with autism spectrum disorder.

Front Pediatr. 2024-5-9

[8]
Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium.

Mol Autism. 2024-5-17

[9]
The gut microbiome and sociability.

Front Neurosci. 2024-4-2

[10]
A digital twin of the infant microbiome to predict neurodevelopmental deficits.

Sci Adv. 2024-4-12

本文引用的文献

[1]
Correlation of distinct behaviors to the modified expression of cerebral Shank1,3 and BDNF in two autistic animal models.

Behav Brain Res. 2021-4-23

[2]
Transcriptional markers of excitation-inhibition balance in germ-free mice show region-specific dysregulation and rescue after bacterial colonization.

J Psychiatr Res. 2021-3

[3]
Autism Spectrum Disorder Associated With Gut Microbiota at Immune, Metabolomic, and Neuroactive Level.

Front Neurosci. 2020-10-8

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Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review.

Rev Psiquiatr Salud Ment (Engl Ed). 2020

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Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux.

Mol Brain. 2020-6-2

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Nuclear Factor Kappa B in Autism Spectrum Disorder: A Systematic Review.

Pharmacol Res. 2020-9

[7]
Dysbiosis of Gut Fungal Microbiota in Children with Autism Spectrum Disorders.

J Autism Dev Disord. 2021-1

[8]
Fecal Microbiota Transplantation in Neurological Disorders.

Front Cell Infect Microbiol. 2020

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MMWR Surveill Summ. 2020-3-27

[10]
Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder.

Microb Ecol. 2020-2-26

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