Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Microb Pathog. 2021 May;154:104826. doi: 10.1016/j.micpath.2021.104826. Epub 2021 Mar 6.
Candida albicans is an opportunistic fungus that can threaten life especially in patients with candidemia. The morbidity and mortality of candidemia originating from a central venous catheter (CVC) and illicit intravenous drug use (IVDU) are increasing. However, the mechanism underlying the bloodborne C. albicans infection remains unclear. Herein, we evaluated the gut microbiome, metabolites and intestinal mucosa by constructing the mouse models with candidemia. Model mice were injected with C. albicans via tail vein. Control mice underwent sham procedures. We observed basic life characteristics, intestinal damage-related alterations using hematoxylin and eosin (H&E) staining, intestinal tight junction protein levels, and intestinal permeability in these mice. Fecal samples were analyzed by performing 16S rRNA gene sequencing of the microbiota and LC-MS metabolomics to reveal the perturbations in intestinal flora and metabolism exacerbating intestinal damage. Weight loss, a decreased survival rate, C. albicans infection spread, and colonic epithelial damage occurred in the model group. Furthermore, the intestinal flora abundance was reduced. Several probiotics, such as Lactobacillus, and butyrate-producing bacteria, including Roseburia, Lachnospiraceae, and Clostridia, were depleted, and some pathogenic bacteria, such as Escherichia-Shigella and Proteus, belonging to the Proteobacteria phylum, and the inflammation mediators Ruminococcus and Parabacteroides were enriched in model mice. Multiple differentially altered metabolic pathways were observed and mainly related to bile acid, arachidonic acid, bile secretion, and arachidonic acid metabolism. This study illustrated the effects of a bloodborne C. albicans on the intestinal microbiota, metabolites, and intestinal barrier, which may provide new insights into tests or treatments for candidemia originating from CVC or IVDU.
白色念珠菌是一种机会性真菌，尤其会对患有念珠菌血症的患者的生命构成威胁。由中心静脉导管（CVC）和非法静脉注射药物（IVDU）引起的念珠菌血症的发病率和死亡率正在上升。然而，血液传播的白色念珠菌感染的机制尚不清楚。在此，我们通过构建念珠菌血症小鼠模型来评估肠道微生物组、代谢物和肠黏膜。通过尾静脉向模型小鼠注射白色念珠菌，对照组小鼠接受假手术。我们观察这些小鼠的基本生命特征、苏木精和伊红（H&E）染色观察肠道损伤相关变化、肠道紧密连接蛋白水平和肠道通透性。通过对肠道微生物组进行 16S rRNA 基因测序和 LC-MS 代谢组学分析，分析粪便样本，以揭示肠道菌群和代谢物的失调，这些失调会加剧肠道损伤。模型组小鼠出现体重减轻、存活率降低、白色念珠菌感染扩散和结肠上皮损伤。此外，肠道菌群丰度减少。一些益生菌，如乳杆菌和产丁酸菌，包括罗斯伯里氏菌、毛螺菌科和梭菌科，被消耗，而一些病原菌，如属于变形菌门的大肠杆菌-志贺氏菌和变形菌，以及炎症介质 Ruminococcus 和 Parabacteroides，在模型小鼠中富集。观察到多个差异改变的代谢途径，主要与胆汁酸、花生四烯酸、胆汁分泌和花生四烯酸代谢有关。本研究说明了血液传播的白色念珠菌对肠道微生物群、代谢物和肠道屏障的影响，这可能为 CVC 或 IVDU 引起的念珠菌血症的检测或治疗提供新的思路。
