Bile Acid Regulates the Colonization and Dissemination of Candida albicans from the Gastrointestinal Tract by Controlling Host Defense System and Microbiota

Abstract

Candida albicans (CA), a commensal and opportunistic eukaryotic organism, frequently inhabits the gastrointestinal (GI) tract and causes life-threatening infections. Antibiotic-induced gut dysbiosis is a major risk factor for increased CA colonization and dissemination from the GI tract. We identified a significant increase of taurocholic acid (TCA), a major bile acid in antibiotic-treated mice susceptible to CA infection. In vivo findings indicate that administration of TCA through drinking water is sufficient to induce colonization and dissemination of CA in wild-type and immunosuppressed mice. Treatment with TCA significantly reduced mRNA expression of immune genes ang4 and Cxcr3 in the colon. In addition, TCA significantly decreased the relative abundance of three culturable species of commensal bacteria, Turicibacter sanguinis, Lactobacillus johnsonii, and Clostridium celatum, in both cecal contents and mucosal scrapings from the colon. Taken together, our results indicate that TCA promotes fungal colonization and dissemination of CA from the GI tract by controlling the host defense system and intestinal microbiota that play a critical role in regulating CA in the intestine.

Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control Candida albicans in the Intestine

“…Dysregulation in host immunity and (or) gut microbiota dysbiosis are the major predisposing factors that contribute to increased CA colonization and (or) dissemination from the intestine [ 6 , 7 , 8 , 9 , 10 ]. Therefore, understanding the factors that regulate CA colonization and dissemination will lead to the identification of novel approaches to prevent and treat life-threatening fungal infections in humans [ 11 , 12 , 13 , 14 ]. To address this gap in the knowledge, we utilize a combination of targeted metabolomics, 16S ribosomal RNA amplicon gene sequencing, and in-vivo mouse models of CA infection to identify the metabolites, microbiome, and host factors regulating CA colonization in the intestine [ 13 , 14 ].…”

“…Our previous findings indicate that taurocholic acid ( TCA ), a major bile acid present in both humans and mice, controls the balance between commensalism and invasive CA infection originating from the gut [ 14 ]. Oral administration of TCA through drinking water is sufficient to induce CA colonization and dissemination from the intestine, even in the absence of antibiotic and (or) immunosuppressive treatment [ 14 ].…”

“…Our previous findings indicate that taurocholic acid ( TCA ), a major bile acid present in both humans and mice, controls the balance between commensalism and invasive CA infection originating from the gut [ 14 ]. Oral administration of TCA through drinking water is sufficient to induce CA colonization and dissemination from the intestine, even in the absence of antibiotic and (or) immunosuppressive treatment [ 14 ]. Furthermore, TCA alters the relative abundance of certain commensal bacterial members and the expression of antifungal peptides in the colon of mice that had increased fungal colonization and dissemination [ 14 ].…”

“…Oral administration of TCA through drinking water is sufficient to induce CA colonization and dissemination from the intestine, even in the absence of antibiotic and (or) immunosuppressive treatment [ 14 ]. Furthermore, TCA alters the relative abundance of certain commensal bacterial members and the expression of antifungal peptides in the colon of mice that had increased fungal colonization and dissemination [ 14 ]. Since innate (neutrophils and macrophages) and adaptive immune cells (T helper 1 and 17 cells) contribute to antifungal defense in the intestine [ 5 , 8 , 15 , 16 ], we aim to understand if TCA dysregulates mucosal immune response to promote CA colonization in the intestine.…”

Systems Biology in Fungal Research

“…For instance, upon antibiotic treatment, which causes dysbiosis of the gastrointestinal tract, a disruption in the commensal relationship between the host and fungal pathogen, Candida albicans , can be observed. One effect is a significant increase in the production of a major bile acid (i.e., taurocholic acid,) which enhances susceptibility of mice to C. albicans infection by inducing colonization and dissemination of the fungi throughout the host [ 10 ]. The study also showed a change in the commensal bacterial population within the gastrointestinal tract of the host upon taurocholic acid treatment, which supports the regulatory role commensal bacteria play in promoting host homeostasis in the presence of fungal pathogens.…”