Dataset Information

Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection

ABSTRACT: 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Trace DSQ quadrupole (Thermo Electron)

SUBMITTER: Wanchao Hu

PROVIDER: MTBLS1918 | MetaboLights | 2021-04-13

REPOSITORIES: MetaboLights

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Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection.

Hu Wanchao W Xu Dan D Zhou Ziyang Z Zhu Junfeng J Wang Dan D Tang Jianguo J

Microbial pathogenesis 20210306

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. ...[more]

PMID: 33689815

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Project description:The intestinal microflora and metabolites produced by these microbes serve as important regulators of the development of sepsis. Accordingly, this study was designed to systematically explore the relationships between the regulation of septicemia and both the intestinal flora and fecal metabolites by examining the functional roles of metabolites in the protection against sepsis-associated intestinal damage. To that end, fecal and peripheral blood mononuclear cell (PBMC) samples were collected from sepsis patients and healthy controls. A series of longitudinal multi-omics analyses were then used to assess the links between the intestinal flora or associated metabolites and PBMCs in sepsis patients, while animal model studies were further used to probe the protective effects of intestinal flora-derived metabolites on intestinal damage and immunity in the context of sepsis. These analyses revealed that intestinal dysbiosis was a common finding in sepsis patients, which commonly exhibited higher levels of deleterious bacteria and/or reductions in beneficial bacteria. A machine learning approach was used to identify samples from sepsis patients, revealing that at the genus level, sepsis samples could be distinguished by the presence of Bifidobacterium, Bacteroides, Porphyromonas, Prevotell, Enterococcus, Anaerococcus and Veillonella species. Metabolomics analyses indicated that there were significant differences in the levels of intestinal flora-derived metabolites including L-serine, L-valine and L-tyrosine when comparing samples from the sepsis and control groups, while corresponding transcriptomic analyses of PBMC samples using an ImmunecellAI analytical approach revealed a significant sepsis-related increase in the abundance of T cells and Th17 cells. Single-cell sequencing data from sepsis-associated PBMCs was also downloaded from the GEO database, confirming the observation that Th17 cell levels and those of other immune cells rose significantly in the context of septicemia. Animal model experiments revealed that intestinal microbiota-derived L-valine was able to alleviate inflammation and protest against sepsis-induced intestinal damage by inhibiting Th17 cell activation. Overall, these results thus highlight the successful application of machine learning to distinguish between sepsis and control samples based on the composition of the intestinal flora while demonstrating the potential therapeutic benefits of L-valine as an inhibitor of Th17 cell activity that may offer value as a means of alleviating or preventing intestinal damage in treated individuals.

Dataset Information

Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection

Publications

Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection.

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