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

Abstract

ABSTRACTCandida albicansis the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemicC. albicansinfections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to preventC. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization ofC. albicans. Our results indicate that cefoperazone-treated mice susceptible toC. albicansinfection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, usingin vivoconcentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development ofC. albicans in vitro. Collectively, results from this study demonstrate that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization ofC. albicans.