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Influence of Fluconazole Administration on Gut Microbiome, Intestinal Barrier, and Immune Response in Mice
Xing Heng1, Yuanhe Jiang1, Weihua Chu2
1School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
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, Firmicutes and Proteobacteria significantly increased, while Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes 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.
Insights
The antifungal fluconazole significantly alters gut microbiota diversity and composition in mice. This gut microbiome change impacts host immune responses, highlighting the importance of a healthy gut microbiome.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Antibiotics are crucial for treating infections but can negatively impact host health.
- Antibiotic use can alter the gut microbiota, potentially affecting the host immune system.
Purpose of the Study:
- To investigate the influence of antifungal (fluconazole) treatment on the gut microbiota and immune system of mice.
- To understand how fluconazole affects bacterial and fungal communities in the gut.
- To assess the impact of fluconazole on host immune markers and gut barrier function.
Main Methods:
- Mice were treated with fluconazole.
- Gut microbiota composition was analyzed (bacteriome and mycobiome).
- Gene expression of immune and barrier function markers (e.g., ZO-1, occludin, MyD88, IL-1β, IL-6) was measured using RT-qPCR.
- Serum levels of immune components (e.g., IL-2, LZM, IgM, IgG) were quantified.
Main Results:
- Fluconazole significantly altered gut microbial composition, reducing bacterial diversity.
- Specific bacterial phyla showed significant changes: increased Firmicutes and Proteobacteria, decreased Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes.
- Mycobiome analysis revealed decreased Ascomycota and increased Mucoromycota.
- Fluconazole treatment decreased the expression of ZO-1, occludin, MyD88, IL-1β, and IL-6.
- Serum levels showed increased IL-2, LZM, and IgM, but decreased IgG.
Conclusions:
- Fluconazole administration significantly impacts the gut microbiota composition and diversity in mice.
- Changes in the gut microbiome induced by fluconazole are associated with altered host immune responses and potentially compromised gut barrier function.
- These findings underscore the critical role of a healthy gut microbiome in maintaining host immune homeostasis.
