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多发性硬化症病毒模型中的肠道微生物群:口服抗生素治疗的调节作用与陷阱

Gut Microbiota in a Viral Model of Multiple Sclerosis: Modulation and Pitfalls by Oral Antibiotic Treatment.

作者信息

Ahmad Ijaz, Omura Seiichi, Khadka Sundar, Sato Fumitaka, Park Ah-Mee, Rimal Sandesh, Tsunoda Ikuo

机构信息

Department of Microbiology, Faculty of Medicine, Kindai University, 377-2 Ohnohigashi, Osakasayma 589-8511, Osaka, Japan.

Department of Medicine, Duke University, Durham, NC 27708, USA.

出版信息

Cells. 2025 Jun 9;14(12):871. doi: 10.3390/cells14120871.

DOI:10.3390/cells14120871
PMID:40558498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12190502/
Abstract

Viral infections have been associated with multiple sclerosis (MS), an immune-mediated disease in the central nervous system (CNS). Since Theiler's murine encephalomyelitis virus (TMEV) can induce MS-like demyelination, TMEV infection is the most widely used viral model for MS. Although the precise pathophysiology is unknown, altered fecal bacterial populations were associated with distinct immune gene expressions in the CNS. We aimed to determine the role of gut microbiota in TMEV infection by administering an antibiotic cocktail in drinking water before (prophylactic administration) or after (therapeutic administration) TMEV infection. The antibiotic administration reduced total eubacteria, including the phyla and , but increased the phylum in feces. Prophylactic administration did not alter TMEV-induced inflammatory demyelination clinically or histologically, without changes in anti-viral IgG1/IgG2c levels or lymphoproliferative responses; therapeutic administration temporarily suppressed the neurological signs. Although antibiotic treatment had minimal effects on TMEV infection, adding metronidazole and ampicillin in drinking water substantially reduced water intake in the antibiotic group of mice, resulting in significant body weight loss. Since dehydration and stress could affect immune responses and gut microbiota, caution should be exercised when planning or evaluating the oral antibiotic cocktail treatment in experimental animals.

摘要

病毒感染与多发性硬化症(MS)有关,MS是一种中枢神经系统(CNS)的免疫介导疾病。由于泰勒氏鼠脑脊髓炎病毒(TMEV)可诱发类似MS的脱髓鞘病变,TMEV感染是MS最常用的病毒模型。尽管确切的病理生理学尚不清楚,但粪便细菌菌群的改变与CNS中不同的免疫基因表达有关。我们旨在通过在TMEV感染前(预防性给药)或感染后(治疗性给药)在饮用水中添加抗生素鸡尾酒来确定肠道微生物群在TMEV感染中的作用。抗生素给药减少了粪便中的总真细菌,包括厚壁菌门和拟杆菌门,但增加了放线菌门。预防性给药在临床或组织学上并未改变TMEV诱导的炎性脱髓鞘,抗病毒IgG1/IgG2c水平或淋巴细胞增殖反应也没有变化;治疗性给药暂时抑制了神经症状。尽管抗生素治疗对TMEV感染影响极小,但在饮用水中添加甲硝唑和氨苄青霉素会显著降低抗生素组小鼠的饮水量,导致体重明显减轻。由于脱水和应激会影响免疫反应和肠道微生物群,因此在计划或评估实验动物口服抗生素鸡尾酒治疗时应谨慎行事。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/da5fda4e2fec/cells-14-00871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/2128da670350/cells-14-00871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/1e8e4a92c8f5/cells-14-00871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/69dcd4fadc65/cells-14-00871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/836aed3d4b61/cells-14-00871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/da5fda4e2fec/cells-14-00871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/2128da670350/cells-14-00871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/1e8e4a92c8f5/cells-14-00871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/69dcd4fadc65/cells-14-00871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/836aed3d4b61/cells-14-00871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3a5/12190502/da5fda4e2fec/cells-14-00871-g005.jpg

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本文引用的文献

1
Restoration of gut integrity by Bacteroides acidifaciens in water-deprived conditions.在缺水条件下,嗜酸拟杆菌对肠道完整性的恢复作用。
Biochem Biophys Res Commun. 2025 Jun 30;767:151917. doi: 10.1016/j.bbrc.2025.151917. Epub 2025 Apr 28.
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Specific microbial ratio in the gut microbiome is associated with multiple sclerosis.肠道微生物群中的特定微生物比例与多发性硬化症有关。
Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2413953122. doi: 10.1073/pnas.2413953122. Epub 2025 Mar 3.
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Alternations of the gut microbiota and the Firmicutes/Bacteroidetes ratio after biologic treatment in inflammatory bowel disease.
炎症性肠病生物治疗后肠道微生物群及厚壁菌门/拟杆菌门比例的变化
J Microbiol Immunol Infect. 2025 Feb;58(1):62-69. doi: 10.1016/j.jmii.2024.09.006. Epub 2024 Oct 1.
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Contribution of microglia/macrophage to the pathogenesis of TMEV infection in the central nervous system.小胶质细胞/巨噬细胞对中枢神经系统中TMEV感染发病机制的作用。
Front Microbiol. 2024 Aug 2;15:1452390. doi: 10.3389/fmicb.2024.1452390. eCollection 2024.
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Application of Theiler's murine encephalomyelitis virus in treatment of multiple sclerosis.泰勒氏鼠脑脊髓炎病毒在多发性硬化症治疗中的应用。
Front Microbiol. 2024 Jun 26;15:1415365. doi: 10.3389/fmicb.2024.1415365. eCollection 2024.
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Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.基于细胞类型的受体和酶反应视角下,肠道微生物群代谢物在脑功能和病理学中的信使作用
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Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis.探讨血小板在病毒诱导的炎症性脱髓鞘疾病和心肌炎中的作用。
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