Effects of Short-Chain Fatty Acid Combinations Relevant to the Healthy and Dysbiotic Gut upon Candida albicans

The major fungal pathogen, Candida albicans, exists as a commensal in the gastrointestinal tract of healthy humans. Fungal colonisation levels increase during gut dysbiosis, when the local microbiota and short-chain fatty acid (SCFA) concentrations become perturbed. Individually, acetic, propionic and butyric acids are reported to exert differential effects on C. albicans. In this study, we tested whether combinations of these SCFAs, at concentrations that broadly reflect healthy and dysbiotic gut profiles, influence virulence-related phenotypes. The selected healthy and dysbiotic SCFA mixes slowed the growth of C. albicans SC5314, increased resistance to cell wall stresses (Calcofluor White, SDS, caspofungin), differentially affected the exposure of the key cell surface pathogen-associated molecular patterns (PAMPs) β-1,3-glucan, chitin and mannan, and influenced total chitin content compared with non-SCFA controls. However, few differences were observed between the healthy and dysbiotic mixes. Furthermore, comparison of isolates from other epidemiological clades revealed that most effects of the SCFA mixes were strain-specific, reflecting the high degree of phenotypic variation reported previously between clinical isolates. Interestingly, the healthy SCFA mix inhibited hyphal development to a greater extent than the dysbiotic mix in some C. albicans isolates including SC5314. This was not reflected in differential adhesion to Caco-2 cells or in altered virulence in the Galleria model of systemic candidiasis. We conclude that SCFA mixtures reflecting those present in the human gut subtly influence some virulence-related phenotypes in C. albicans in a strain-specific manner.