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氟康唑给药对小鼠肠道微生物组、肠道屏障和免疫反应的影响。

Influence of Fluconazole Administration on Gut Microbiome, Intestinal Barrier, and Immune Response in Mice.

机构信息

School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

School of Life Science and Technology, China Pharmaceutical University, Nanjing, China

出版信息

Antimicrob Agents Chemother. 2021 May 18;65(6). doi: 10.1128/AAC.02552-20.

Abstract

Antibiotics that can treat or prevent infectious diseases play an important role in medical therapy. However, the use of antibiotics has potentially negative effects on the health of the host. For example, antibiotics use may affect the host's immune system by altering the gut microbiota. Therefore, the aim of the study was to investigate the influence of antifungal (fluconazole) treatment on the gut microbiota and immune system of mice. Results showed that the gut microbial composition of mice receiving fluconazole treatment was significantly changed after the trial. Fluconazole did not affect the relative abundance of bacteria but significantly reduced the diversity of bacterial flora. In the bacteriome, and significantly increased, while , , and showed a remarkable reduction in the fluconazole-treated group compared with the control group. In the mycobiome, the relative abundance of Ascomycota was significantly decreased and Mucoromycota was significantly increased in the intestine of mice treated with fluconazole compared to the control group. Reverse transcription-quantitative PCR (RT-qPCR) results showed that the relative gene expression of ZO-1, occludin, MyD88, interleukin-1β (IL-1β), and IL-6 was decreased in the fluconazole-treated group compared to the control. Serum levels of IL-2, LZM, and IgM were significantly increased, while the IgG level was considerably downregulated in the fluconazole-treated compared to the control group. These results suggest that the administration of fluconazole can influence the gut microbiota and that a healthy gut microbiome is important for the regulation of the host immune responses.

摘要

抗生素在医学治疗中具有重要作用,可以治疗或预防传染病。然而,抗生素的使用可能对宿主的健康产生潜在的负面影响。例如,抗生素的使用可能通过改变肠道微生物群来影响宿主的免疫系统。因此,本研究旨在探讨抗真菌药物(氟康唑)治疗对小鼠肠道微生物群和免疫系统的影响。结果表明,接受氟康唑治疗的小鼠肠道微生物组成在试验后发生了显著变化。氟康唑不影响细菌的相对丰度,但显著降低了细菌菌群的多样性。在细菌组中, 和 显著增加,而 、 和 在氟康唑治疗组中与对照组相比显著减少。在真菌组中,与对照组相比,氟康唑处理组小鼠肠道中子囊菌门的相对丰度显著降低,而毛霉门的相对丰度显著增加。逆转录定量 PCR (RT-qPCR) 结果显示,与对照组相比,氟康唑治疗组中 ZO-1、occludin、MyD88、白细胞介素-1β (IL-1β) 和 IL-6 的相对基因表达降低。与对照组相比,氟康唑治疗组血清中 IL-2、LZM 和 IgM 水平显著升高,而 IgG 水平显著下调。这些结果表明,氟康唑的给药可以影响肠道微生物群,而健康的肠道微生物群对于宿主免疫反应的调节很重要。

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