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Vitamin D Improves Klebsiella-Induced Severe Pneumonia in Rats by Regulating Intestinal Microbiota
Jia-Jia Hu1, Yu-Sen Lin1, Jing-Cong Zhang1
1Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Background:
In the context of progressively uncontrolled drug resistance of bacteria, the difficulty of treating Klebsiella (KP)-induced pneumonia increases. Searching for drugs other than antibiotics has become an urgent task. Vitamin D (VD), meanwhile, is shown to be capable of treating pneumonia. Therefore, we aimed to explore the effects and mechanisms of VD on KP-infected rats.
Methods:
Male Sprague Dawley rats were divided into the Control, VD, KP and KP+VD groups. A rat pneumonia model was induced using an intratracheal drop of 2.4×108 CFU/mL KP. VD treatment was performed by gavage using 5 μg/kg. Subsequently, the survival of the rats was recorded, and the lungs, bronchoalveolar lavage fluid, and feces of the rats were collected 4 days after KP infection. Next, the water content of lung tissues was measured by the wet-to-dry weight ratio. Histopathological changes of lung tissues were observed by Hematoxylin and Eosin staining and the levels of inflammatory factors (TNF-α, IL-1β, MCP1) were detected using ELISA. The feces of rats in each group were also subjected to 16S rDNA gene analysis of intestinal microbiota.
Results:
Compared with the KP group, the KP+VD group showed a significant increase in survival, a significant decrease in water content and bacterial counts in the lungs, a significant improvement in lung injury, and a significant decline in the levels of TNF-α, IL-1β, and MCP1. According to the 16S rDNA sequencing, VD altered the structure of the intestinal bacterial community in the KP-infected rats and made the species richness similar to that of healthy rats. Additionally, the abundance of Anaeroglobus was significantly increased in the KP+VD group.
Conclusion:
VD modulates intestinal microbiota to increase the resistance of rats to pneumonia caused by Klebsiella infection.
Insights
Vitamin D (VD) treatment improved survival and reduced lung injury in rats with Klebsiella pneumoniae (KP) pneumonia. VD also modulated the gut microbiota, enhancing resistance to KP infection.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Rising antibiotic resistance necessitates alternative treatments for bacterial infections.
- Klebsiella pneumoniae (KP) induced pneumonia presents a growing therapeutic challenge.
- Vitamin D (VD) has demonstrated potential in treating pneumonia.
Purpose of the Study:
- To investigate the therapeutic effects of Vitamin D (VD) on Klebsiella pneumoniae (KP) induced pneumonia in a rat model.
- To elucidate the underlying mechanisms of VD's action, including its impact on the host immune response and intestinal microbiota.
Main Methods:
- A rat model of Klebsiella pneumoniae (KP) pneumonia was established.
- Rats were treated with Vitamin D (VD) via gavage.
- Survival rates, lung injury (water content, histopathology), inflammatory markers (TNF-α, IL-1β, MCP1), and intestinal microbiota composition (16S rDNA sequencing) were analyzed.
Main Results:
- Vitamin D (VD) treatment significantly increased survival rates in KP-infected rats.
- VD reduced lung water content, bacterial load, and inflammatory cytokine levels.
- VD administration altered the intestinal microbiota structure, increasing species richness and the abundance of Anaeroglobus.
Conclusions:
- Vitamin D (VD) demonstrates significant therapeutic potential against Klebsiella pneumoniae (KP) induced pneumonia.
- VD's efficacy is linked to its ability to modulate the intestinal microbiota, thereby enhancing host resistance.
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