These results, obtained with the use of a primary pIEC model, indicate that HMOs reduce virulence characteristics of C. albicans and suggest a role for HMOs in protecting the premature infant intestine from invasion and damage by C. albicans hyphae.

In premature infants, the opportunistic fungal pathogen Candida albicans is a leading cause of life‐threatening infections; the primary site for invasion being the intestine. The goal of this study was to test the hypothesis that Human Milk Oligosaccharides (HMOs) protect premature intestinal epithelial cells (IEC) from invasion by C. albicans. We used H4 cells, an established, primary, human fetal IEC line and measured fungal invasion immunohistochemically. The presence of HMOs, at concentrations present in human milk, resulted in an ~60% reduction in fungal invasion of H4 cells (p<0.05). Further, the HMO effect on invasion followed a dose‐response relationship. At slightly higher than physiologic concentrations, HMOs decreased the ability of C. albicans to make contact with H4 cells (p<0.05). In addition, at physiologic concentrations and above, HMOs reduced the overall lengths of C. albicans hyphae (p<0.05), the morphology associated with tissue invasion and injury. HMOs did not, however, reduce overall C. albicans growth rates in liquid or on solid growth media. In conclusion, HMOs decrease the ability of C. albicans to invade H4 cells, supporting a protective role for HMOs in the premature intestine. We speculate that this function of HMOs is attributed to their negative effect on C. albicans hyphal growth as well as blockade of physical interactions between host and fungal cells.