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在自闭症的啮齿动物模型中,益生菌与γ-氨基丁酸(GABA)受体的基因表达相关,可减少肠道渗漏:强调肠-脑轴的重要性。

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.

作者信息

Bin-Khattaf Rawan M, Al-Dbass Abeer M, Alonazi Mona, Bhat Ramesa Shafi, Al-Daihan Sooad, El-Ansary Afaf K

机构信息

Biochemistry Department, Science College, King Saud University, P.O. Box 22452, Riyadh, 11495, Saudi Arabia.

Autism Center, Lotus Holistic Medical Center, Abu Dhabi, 110281, United Arab Emirates.

出版信息

Transl Neurosci. 2024 Oct 3;15(1):20220354. doi: 10.1515/tnsci-2022-0354. eCollection 2024 Jan 1.


DOI:10.1515/tnsci-2022-0354
PMID:39380963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11459612/
Abstract

OBJECTIVE: Rodent models may help investigations on the possible link between autism spectrum disorder and increased permeability of the gastrointestinal (GI) tract since autistic patients frequently manifested GI troubles as comorbidities. METHODS: Forty young male western Albino rats, weighing approximately 60-70 g and aged 3-4 weeks, were used. In each of the six experimental groups, eight animals were treated as follows. The mice in the control group (I) received phosphate-buffered saline orally. For 3 days, the animals in the propionic acid (PPA)-treated groups (II and III) were given an oral neurotoxic dose of PPA (250 mg/kg body weight each day). Group II was euthanized after 3 days; however, Group III was left alive to be euthanized alongside the other groups. The animals were kept at 22 ± 1°C and allowed to access water and normal food as needed. Identical dosages of PPA were given to the rats in the three treatment groups (IV, V, and VI), and for 3 weeks, they were given the following treatments: 0.2 g/kg body weight of pure , a probiotic mixture of PROTEXIN®, Somerset, UK and pure , respectively. The six groups underwent measurements of serum zonulin and occludin as variables associated with leaky gut, glutathione, malondialdehyde, and catalase as oxidative stress-related variables, with gamma-aminobutyric acid (GABA) receptor gene expression. RESULTS: This study demonstrated the potential effects of pure or mixed probiotics in lowering zonulin and occludin as markers of increased intestinal permeability, enhancing GABA receptor expression, and reducing oxidative stress as neurotoxic effects of PPA. CONCLUSIONS: This study demonstrates that various probiotics protect gut barrier function and could be used to alleviate increased intestinal permeability caused by oxidative stress and impaired GABA signaling as a result of PPA neurotoxicity, addressing the clinical implications of probiotic supplements.

摘要

目的:啮齿动物模型可能有助于研究自闭症谱系障碍与胃肠道(GI)通透性增加之间的潜在联系,因为自闭症患者经常表现出胃肠道问题作为合并症。 方法:使用40只年轻的雄性西部白化大鼠,体重约60 - 70克,年龄3 - 4周。在六个实验组中,每组八只动物接受如下处理。对照组(I)的小鼠口服磷酸盐缓冲盐水。丙酸(PPA)处理组(II和III)的动物连续3天口服神经毒性剂量的PPA(每天250毫克/千克体重)。II组在3天后安乐死;然而,III组存活下来与其他组一起安乐死。动物饲养在22±1°C,根据需要提供水和正常食物。三个处理组(IV、V和VI)的大鼠给予相同剂量的PPA,并在3周内分别给予以下处理:0.2克/千克体重的纯 、英国萨默塞特的PROTEXIN®益生菌混合物和纯 。六组测量了与肠道渗漏相关的变量血清zonulin和闭合蛋白、与氧化应激相关的变量谷胱甘肽、丙二醛和过氧化氢酶,以及γ-氨基丁酸(GABA)受体基因表达。 结果:本研究证明了纯益生菌或混合益生菌在降低zonulin和闭合蛋白作为肠道通透性增加标志物方面的潜在作用,增强GABA受体表达,并减少PPA神经毒性的氧化应激神经毒性作用。 结论:本研究表明,各种益生菌可保护肠道屏障功能,可用于缓解由氧化应激和PPA神经毒性导致的GABA信号受损引起的肠道通透性增加,探讨了益生菌补充剂的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/11459612/db16b649523e/j_tnsci-2022-0354-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/11459612/c88ad964e834/j_tnsci-2022-0354-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/11459612/db16b649523e/j_tnsci-2022-0354-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/11459612/c88ad964e834/j_tnsci-2022-0354-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/11459612/db16b649523e/j_tnsci-2022-0354-fig002.jpg

相似文献

[1]
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

[2]
Probiotic Ameliorating Effects of Altered GABA/Glutamate Signaling in a Rodent Model of Autism.

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[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]
Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus on .

Nutrients. 2025-7-29

[2]
Serum zonulin level in autistic children and its relation to severity of symptoms a case-control study.

Sci Rep. 2025-7-30

[3]
Impact of GABA and nutritional supplements on neurochemical biomarkers in autism: a PPA rodent model study.

Front Mol Neurosci. 2025-3-18

本文引用的文献

[1]
Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder.

Nutrients. 2023-3-27

[2]
Independent and Combined Effects of Probiotics and Prebiotics as Supplements or Food-Rich Diets on a Propionic-Acid-Induced Rodent Model of Autism Spectrum Disorder.

Metabolites. 2022-12-29

[3]
Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Neurosci Bull. 2023-6

[4]
Gastrointestinal symptoms have a minor impact on autism spectrum disorder and associations with gut microbiota and short-chain fatty acids.

Front Microbiol. 2022-10-7

[5]
Probiotic Ameliorating Effects of Altered GABA/Glutamate Signaling in a Rodent Model of Autism.

Metabolites. 2022-8-4

[6]
Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review.

Nutrients. 2022-4-1

[7]
Probiotics ameliorates LPS induced neuroinflammation injury on Aβ 1-42, APP, γ-β secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes.

Metab Brain Dis. 2022-6

[8]
The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota.

Tissue Barriers. 2022-7-3

[9]
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

[10]
Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease.

Int J Mol Sci. 2021-2-5

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