Secondary bile acids inhibit Candida albicans growth and morphogenesis

Guinan, Jack; Villa, Pedro de la; Thangamani, Shankar

doi:10.1093/femspd/fty038

Cited by 34 publications

(34 citation statements)

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“…The gut microbiota plays a major role in the colonization resistance to enteric bacterial and fungal pathogens including C. albicans 37–45 . While mechanisms of colonization resistance to enteric pathogens by commensal bacteria are speculated to include immune responses, competition for nutrients, pH modulation, and synthesis of antimicrobial and antifungal compounds 29,37–39,44–51 , the mechanisms associated with colonization resistance to C. albicans remain poorly understood. The development of effective preventative and therapeutic treatments thus necessitates a deeper understanding of the innate mechanisms of colonization resistance to C. albicans .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Antibiotic treatment significantly alters SCFA levels in the gut; however, the composition and concentration of other critical gut metabolites including bile acids are also affected 24,25,29,30 . Recently, we have shown that bile acids play an important role in controlling C. albicans growth and morphogenesis 29,30 . We previously demonstrated that treatment with in vivo concentrations of the primary conjugated bile acid taurocholic acid (TCA) (0.0125%) promotes C. albicans growth and morphogenesis, whereas treatment with in vivo concentrations of secondary bile acids deoxycholic acid (DCA [0.05%]) and lithocholic acid (LCA [0.01%]) inhibit C. albicans growth and morphogenesis in vitro 29,30 .…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in the normal levels of microbial-derived bile acids and SCFAs have been implicated in the growth, colonization, and pathogenesis of enteric pathogens including C. difficile 24,25,28 . Moreover, we have recently demonstrated that microbial-derived bile acids play an important role in the GI colonization of C. albicans 29 30 . However, the role of SCFAs including acetate, propionate, and butyrate–three major fatty acids produced by gut microbiota 31–36 –in the GI colonization of C. albicans is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization ofCandida albicans

Thangamani¹,

Guinan²,

Wang

et al. 2018

Preprint

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27Candida albicans is the fourth most common cause of systemic nosocomial infections, 28 posing a significant risk in immunocompromised individuals. As the majority of systemic C. 29 albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the 30 mechanisms associated with GI colonization is essential in the development of novel methods to 31 prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived 32 short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, 33 morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated 34 mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal 35 contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration 36 of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm 37 development of C. albicans in vitro. Collectively, results from this study demonstrate that 38 antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI 39 colonization of C. albicans. 40 41 42 Keywords: C. albicans, antibiotic treatment, SCFAs, gastrointestinal colonization, hyphae and 43 attachment.44 45 46 47 48 49 50C. albicans, often present in the healthy gastrointestinal (GI) tract, is harmless to the 51 immunocompetent human host with its resident microbiota 1,2 . Though compelling evidence 52 suggests that disturbances in immune regulation contribute to invasive C. albicans infections, 53 antibiotic-induced gut dysbiosis remains a major risk factor for increased C. albicans colonization 54 and dissemination in immunocompromised patients and individuals with antibiotic-associated 55 diarrhea (AAD) [3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Administration of broad-spectrum antibiotics increases the risk of C. albicans 56 colonization in the gut and the source of systemic infections is often found to be the GI tract 13,16-57 20 . In addition, more than 60% of individuals with AAD test positive for C. albicans and patients 58 treated with antibiotics for Clostridium difficile often develop an episode of candidemia 9,10,14,15,21 . 59Taken together, these studies demonstrate that antibiotic-induced gut dysbiosis in 60 immunocompromised individuals and AAD patients leads to increased colonization of C. albicans 61 and this increased intestinal colonization predisposes high-risk patients to systemic candidiasis 62 22,23 . Therefore, understanding the factors involved in antibiotic-induced gut dysbiosis and 63 subsequent GI colonization of C. albicans is critical to treat and prevent C. albicans pathogenesis. 64 65Antibiotic treatment in mice and humans alters the composition of gut microbiota, 66 ultimately leading to changes in the levels of microbial-derived gut metabolites, mainly bile acids 67 and short-chain fatty acids (SCFAs) [24][25][26][27][28] . Alterations in the normal levels of microbial-derive...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization ofCandida albicans

Thangamani¹,

Guinan²,

Wang

et al. 2018

Preprint

Self Cite

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show abstract

“…Obviously, they are taken up regularly by mammals as well as humans via food, which may lead to intermittent or even permanent gut colonization even in healthy subjects [1], [5], [19] not least because they are relatively resistant to bile [12] in comparison to Candida albicans being susceptible to bile acids to some extent [20]. …”

Section: Biologymentioning

confidence: 99%