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戒酒辅助药物安塔布司(双硫仑)对C57BL/6小鼠肠道微生物群的扰动。

Perturbations in the gut microbiome of C57BL/6 mice by the sobriety aid Antabuse® (disulfiram).

作者信息

Evans Sarah E, Valentine Meagan E, Gallimore Fallon, Meka Yogesh, Koehler Samuel I, Yu Hongwei D, Valentovic Monica A, Long Timothy E

机构信息

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.

Department of Pharmaceutical Sciences, School of Pharmacy, Marshall University, Huntington, WV 25755, United States.

出版信息

J Appl Microbiol. 2025 Jan 6;136(1). doi: 10.1093/jambio/lxae305.

DOI:10.1093/jambio/lxae305
PMID:39701818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11704607/
Abstract

AIMS

Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.

METHODS AND RESULTS

Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed that disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum, whereas the feces composition in male mice was the most heavily altered.

CONCLUSIONS

Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the minimum inhibitory concentration data for isolates from the human gut microbiota.

摘要

目的

双硫仑(安塔布司®)是一种口服戒酒药物,对革兰氏阳性兼性厌氧菌具有抗菌活性。本研究的目的是测定其对人类肠道微生物群中厌氧菌的抗菌活性,并利用C57BL/6小鼠确定双硫仑改变回肠、盲肠和粪便微生物组成的程度。

方法与结果

通过微量稀释法进行的抗菌药敏试验表明,双硫仑可抑制肠道厌氧菌种拟杆菌属、梭菌属、消化链球菌属和卟啉单胞菌属的体外生长。对处理过的小鼠与未处理的小鼠的回肠、盲肠和粪便内容物中分离出的16S rRNA进行差异测序,结果显示双硫仑可使革兰氏阴性肠道菌群富集。在雌性小鼠中,回肠中的富集最为明显,而雄性小鼠粪便的组成变化最大。

结论

如从人类肠道微生物群分离出的菌株的最低抑菌浓度数据所预测的那样,每日口服双硫仑会使肠道革兰氏阳性厌氧菌数量减少。

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本文引用的文献

1
Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice.双硫仑可减少高脂血症小鼠的动脉粥样硬化并增强噬作用、自噬和动脉保护肠道微生物群。
J Am Heart Assoc. 2024 Apr 16;13(8):e033881. doi: 10.1161/JAHA.123.033881. Epub 2024 Apr 2.
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Overview of Alcohol Use Disorder.酒精使用障碍概述。
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Disulfiram: Mechanisms, Applications, and Challenges.双硫仑:作用机制、应用及挑战
Antibiotics (Basel). 2023 Mar 6;12(3):524. doi: 10.3390/antibiotics12030524.
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Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism.双硫仑通过调节肠道微生物群和胆汁酸代谢改善非酒精性脂肪性肝炎。
Nat Commun. 2022 Nov 11;13(1):6862. doi: 10.1038/s41467-022-34671-1.
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The role of the gut microbiota in health and cardiovascular diseases.肠道微生物群在健康和心血管疾病中的作用。
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Integrated Analysis of the Alterations in Gut Microbiota and Metabolites of Mice Induced After Long-Term Intervention With Different Antibiotics.不同抗生素长期干预后小鼠肠道微生物群和代谢产物变化的综合分析
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Disulfiram: A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.双硫仑:一种用于治疗传染病的处于临床前和临床开发阶段的重新利用药物。
Antiinfect Agents. 2022 Jun;20(3). doi: 10.2174/2211352520666220104104747. Epub 2022 Apr 27.
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Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives.用于胃肠道健康的乳杆菌属:当前和未来的观点。
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Med Mycol. 2022 Mar 17;60(4). doi: 10.1093/mmy/myac016.
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