Effects of fungal colonization on the host

Carol Kumamoto PhD

Department of Molecular Biology and Microbiology Tufts University

The opportunistic fungal pathogen Candida albicans is often found as a component of the normal human gut microbiota. Intestinal colonization by this organism is significant because organisms colonizing a host as commensals are the source of organisms that produce invasive infection in a compromised host. In a murine model, we demonstrated that C. albicans populations detect host immune status, allowing the colonizing fungal cells to modify their gene expression depending on host immune status.

The intricate regulation of C. albicans colonization suggested that the biology of the host and the fungus are closely tied together and we therefore investigated effects of C. albicans colonization on host biology. We found that C. albicans pre-colonization protected antibiotic-treated mice from lethal challenge with the bacterial pathogen Clostridioides difficile. These effects were mediated, at least in part, by alteration of the immune response and the gut metabolome.

To determine whether C. albicans gut colonization affected host physiology beyond the gut, we investigated its effects on the gut-brain axis, the bidirectional communication that connects the gut and brain. We found that the presence of C. albicans in the gut microbiota of mice altered the endocannabinoid system and resulted in increased anxiety-like behavior and dysregulation of circadian regulation. These findings show wide-ranging effects on the host as a consequence of C. albicans gut colonization.