Dietary tannic acid promotes intestinal clearance of C. albicans by cross-linking hyphal chitosan.

Intestinal Candida overgrowth is the major cause of candidemia in intensive care patients. The lack of phytogenic bioactive components in parenteral nutrition inspired us to focus on the role of polyphenols in preventing intestinal Candida albicans overgrowth. Here, we found that tannic acid (TA), which is abundant in tea, coffee, fruit and vegetables, promoted the clearance of C. albicans from feces and increased the survival rate of mice by about 60%. Interestingly, an opposite mechanism of TA-induced hyphal aggregation was observed. The main target of TA was identified as chitosan, which constitutes less than 5‰ of the dry weight of the cell wall. The combination of TA and chitosan effectively reduces the invasion and cytotoxicity of Candida albicans hyphae on host cells. As a previously neglected component, chitosan is mainly produced by the chitin deacetylase Cda2. Our results elucidate the essential role of Cda2 in modulating chitin and chitosan levels, as well as in maintaining the stress responses and virulence in C. albicans, suggesting its potential as a target for new antifungal therapies. The protective role of TA indicates that a plant-based diet is critical for intestinal defense against C. albicans pathogenesis, which may develop into new strategies to prevent candidemia.