Diet-responsive genetic determinants of intestinal colonization in the yeast <i>Candida albicans</i>

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast <i>Candida albicans</i> colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by <i>C. albicans</i> and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for <i>C. albicans</i> to colonize the high oleic acid diet-fed mice. 16S rRNA analysis detected rather modest differences in the bacterial communities between control and oleic acid-rich diets. We identified <i>SOK1</i> as an oleic acid-induced kinase that dictates cell wall mannan exposure and binding to intestinal mucin under anaerobic conditions. Furthermore, oleic acid induced the expression of several <i>C. albicans</i> transcription factors that positively regulate intestinal colonization via remodeling of the fungal cell surface. We posit that in environments largely devoid of oxygen like the large intestine, dietary oleic acid favors a <i>C. albicans</i> cell surface configuration that enhances gut occupation.IMPORTANCE<i>Candida albicans</i> is a fungal pathobiont that inhabits the digestive tract of most human adults. The fungus has roles in health and disease because it modulates prominent immune-inflammatory host responses from the gut, and in individuals with debilitated defenses, it can disseminate from the gastrointestinal tract, producing life-threatening infections. Here, we investigate how a dietary component shapes <i>C. albicans</i> physiology and ultimately its ability to inhabit the mammalian gut.