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

Shankar Thangamani,Harm Hogenesch,Tony R Hazbun,Vijay Antharam,Yan Jin,Haiwei Gu,Ross Monasky,Jung Keun Lee,Grace L Guo

doi:10.3390/jof7121030

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.

Highlights

IntroductionCandida albicans (CA) is normally absent in the GI tract of adult mice; antibiotic treatment leads to CA colonization and dissemination in mice, and closely resembles CA infection in human patients [5,6,14,15,16,17,18,19,20,21,22]
Only the abundance of taurocholic acid (TCA) was significantly higher than all other bile acid metabolites that were increased in the antibiotic-treated Candida albicans (CA) susceptible mice compared to untreated control groups (Figure 1D)
These results indicate that TCA is the highly up-regulated bile acid in the antibiotic-treated CA- susceptible mice compared to control groups

Summary

Introduction

CA is normally absent in the GI tract of adult mice; antibiotic treatment leads to CA colonization and dissemination in mice, and closely resembles CA infection in human patients [5,6,14,15,16,17,18,19,20,21,22]. Because colonization of the GI tract is necessary for the dissemination of CA, and CA colonization resistance is nullified by antibiotic treatment, identifying the factors that play a critical role in CA colonization may pave the way to develop novel approaches to limit CA dissemination [6,20]

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Results

Conclusion