Vitamin D Improves Klebsiella-Induced Severe Pneumonia in Rats by Regulating Intestinal Microbiota

Jia-Jia Hu,* Yu-Sen Lin,* Jing-Cong Zhang, Yan-Hong Wang Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Hong Wang, Email wangyh28@mail.sysu.edu.cnBackground: 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.Keywords: severe pneumonia, Klebsiella, intestinal microbiota, vitamin D