Ablation of Gut Microbiota Alleviates DON-Induced Neurobehavioral Abnormalities and Brain Damage in Mice.

IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Toxins Pub Date : 2025-03-18 DOI:10.3390/toxins17030144
Yujing Cui, Samuel Kumi Okyere, Haoyue Guan, Zixuan Hua, Youtian Deng, Huidan Deng, Junliang Deng
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Abstract

Background: Deoxynivalenol (DON) poses a threat to animal and human health, particularly causing damage to the nervous system. Intestinal flora can regulate the nervous system through the gut-brain axis; however, there is currently a lack of evidence on the effect of changing the intestinal flora on the damage to the nervous system caused by DON. Therefore, this study aims to investigate the effect of gut microbiota ablation on neurotoxicity induced by exposure to deoxynivalenol.

Methods: One hundred-twenty (120) specific pathogen-free (SPF) male C57BL/6j mice were randomly divided into four groups (control group, microbiota-uncleaned group + 5 mg/kg/BW DON, microbiota-cleared group, and microbiota-cleared group + 5 mg/kg/BW DON). The open field and Morris behavior tests were used to evaluate behavior changes after DON exposure. After 14 days of treatment, the mice were euthanized and brain tissues were collected for further analysis.

Results: The tests showed that DON exposure led to anxiety and decreased learning ability in mice with no gut microbiota ablation. We also observed pathological changes including neuronal shrinkage, degeneration, and cortical edema in the mice with no microbiota ablation after DON exposure. In addition, the protein and mRNA levels of tight junction proteins and anti-inflammatory factors were decreased in the mice with no microbiota ablation after DON exposure compared with mice with ablated microbiota.

Conclusions: We concluded that the presence of microbiota plays a key role in the neurotoxicity induced by DON; thus, ablation of the intestinal microbiota can effectively improve brain damage caused by DON.

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肠道菌群消融减轻don诱导的小鼠神经行为异常和脑损伤。
脱氧雪腐镰刀菌醇(DON)对动物和人类健康构成威胁,特别是对神经系统造成损害。肠道菌群可通过肠脑轴调节神经系统;然而,改变肠道菌群对DON引起的神经系统损伤的影响,目前缺乏证据。因此,本研究旨在探讨肠道微生物群消融对脱氧雪腐镰刀菌醇暴露引起的神经毒性的影响。方法:120只SPF雄性C57BL/6j小鼠随机分为4组(对照组、未清洗微生物组+ 5 mg/kg/BW DON、清除微生物组和清除微生物组+ 5 mg/kg/BW DON)。采用open field和Morris行为试验评价DON暴露后的行为变化。治疗14天后,对小鼠实施安乐死,并收集脑组织作进一步分析。结果:实验表明,在没有肠道微生物群消融的情况下,DON暴露会导致小鼠焦虑和学习能力下降。我们还观察到在DON暴露后,没有微生物群消融的小鼠的病理变化,包括神经元萎缩、变性和皮质水肿。此外,与微生物群消融的小鼠相比,未消融的小鼠DON暴露后紧密连接蛋白和抗炎因子的蛋白质和mRNA水平降低。结论:微生物群的存在在DON诱导的神经毒性中起关键作用;因此,肠道菌群消融可有效改善DON所致脑损伤。
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来源期刊
Toxins
Toxins TOXICOLOGY-
CiteScore
7.50
自引率
16.70%
发文量
765
审稿时长
16.24 days
期刊介绍: Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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