bCandida albicans is the leading cause of fungal infections; but it is also a member of the human microbiome, an ecosystem of thousands of microbial species potentially influencing the outcome of host-fungal interactions. Accordingly, antibacterial therapy raises the risk of candidiasis, yet the underlying mechanism is currently not fully understood. We hypothesize the existence of bacterial metabolites that normally control C. albicans growth and of fungal resistance mechanisms against these metabolites. Among the most abundant microbiota-derived metabolites found on human mucosal surfaces are weak organic acids (WOAs), such as acetic, propionic, butyric, and lactic acid. Here, we used quantitative growth assays to investigate the dose-dependent fungistatic properties of WOAs on C. albicans growth and found inhibition of growth to occur at physiologically relevant concentrations and pH values. This effect was conserved across distantly related fungal species both inside and outside the CTG clade. We next screened a library of transcription factor mutants and identified several genes required for the resistance of C. albicans to one or more WOAs. A single gene, MIG1, previously known for its role in glucose repression, conferred resistance against all four acids tested. Consistent with glucose being an upstream activator of Mig1p, the presence of this carbon source was required for WOA resistance in wild-type C. albicans. Conversely, a MIG1-complemented strain completely restored the glucose-dependent resistance against WOAs. We conclude that Mig1p plays a central role in orchestrating a transcriptional program to fight against the fungistatic effect of this class of highly abundant metabolites produced by the gastrointestinal tract microbiota.O ver 60% of fungal infections are caused by Candida albicans, and these infections range from debilitating skin or mucosal infections to potentially lethal disseminated disease, most especially in immunocompromised individuals and in nosocomial settings (1, 2). At the same time, this species is also the fungus most frequently isolated from the oral cavity, the vaginal mucosa, and the gastrointestinal (GI) tract of most healthy individuals (2), indicating a commensal nature of the host-microbe interaction in unperturbed conditions. A switch from asymptomatic colonization to opportunistic infection is supported by evidence of strain relatedness between C. albicans isolates from blood cultures and from the GI tract of the same patients (3). Hence, controlling C. albicans growth in the GI tract might limit one of the primary sources of systemic candidiasis.Antibiotic treatment, which is well known to profoundly modify the GI microbiome (4, 5), is a strong risk factor for both vulvovaginal and systemic candidiasis in humans (6, 7). Moreover, most mouse models of C. albicans GI colonization rely on oral antibiotic treatment (8-10). Other models rely on the use of germfree mice (11), infant mice (12, 13), which harbor a significantly different GI microbiome than adults (14), or ...