Gastrointestinal anaerobes and Enterococcus faecalis promote Candida glabrata gastrointestinal colonization and organ dissemination.

Abstract

Background: Candida glabrata is a common causative pathogen of endogenous candidiasis. It is assumed that the gastrointestinal flora affects C. glabrata gastrointestinal colonization and organ dissemination in the gastrointestinal tract (GIT). However, no reports have yet described the relationships between C. glabrata and bacteria in the GIT. This study aimed to clarify these relationships using a mouse endogenous candidiasis model with cortisone acetate immunosuppression.

Methods: Dysbiosis was induced in the GIT by several antibiotic combinations, and then C. glabrata gastrointestinal colonization and organ dissemination were evaluated. Next, metagenomic sequencing analysis of the gastrointestinal flora was performed to identify bacteria associated with C. glabrata organ dissemination. Finally, coinfection experiments were performed using bacteria isolated from the mouse GIT.

Results: C. glabrata organ dissemination was significantly promoted using specific antibiotics regardless of the amount of colonization in the GIT. Metagenomic sequencing analysis of the gastrointestinal flora showed that Enterococcus species and anaerobes were significantly associated with enhanced organ dissemination, whereas Enterobacterales, such as Escherichia species and Klebsiella species, were associated with the suppression of organ dissemination. In coinfection experiments, Enterococcus faecalis and Faecalibaculum rodentium inoculation, but not either of them, increased C. glabrata organ dissemination without affecting gastrointestinal colonization.

Conclusions: Coinfection with gastrointestinal bacteria promoted C. glabrata organ dissemination, which would indicate that gastrointestinal flora could affect C. glabrata dissemination. Therefore, the gastrointestinal flora could be a target for intervention or treatment in clinical settings. Insights from this study would lead to better control of endogenous candidiasis focusing on the gastrointestinal flora.