Study Identifies Key Factors Enabling Candida albicans to Colonize the Gut

About 80% of people carry the fungus Candida albicans in their gut, largely without any apparent symptoms or health issues. Nevertheless, this common microorganism can, under certain conditions, transform into an agent that causes serious diseases affecting multiple organs such as the urinary tract, lungs, and brain. To understand how C. albicans is able to establish residence in the gut, a team led by scientists at Baylor College of Medicine used a mouse model to investigate the process. Their findings were recently published in Microbiology Spectrum. 

First author Kelsey Mauk explained that previous research typically relied on mouse models treated with antibiotics or drugs that suppress the immune system before introducing C. albicans. These treatments were believed to be necessary for successful colonization, as the common understanding was that the fungus would not be able to persist in the gut without a compromised immune system or altered microbiome. However, Mauk and colleagues chose to study colonization in mice with healthy, unaltered conditions to better emulate real-life scenarios.

Contrary to their expectations, the researchers found that a clinical strain of C. albicans, called CLCA10, was able to not only establish itself but also persist in the guts of healthy mice for at least 58 days. This colonization did not result in weight loss, inflammation, or major disruptions in the bacterial microbiome. In addition, anti-fungal drug treatments reduced the presence of the fungus but did not completely eliminate it. Upon investigation, C. albicans was found to be mostly associated with the contents of the gut and its mucus layer. Other human-associated fungal species, when introduced to the mouse gut, could not achieve similar persistence, suggesting a unique capacity of C. albicans.

The team had anticipated that mouse-specific factors—such as the animal’s sex, diet, or source—might affect colonization, but, as Mauk stated, “none of these factors affected the ability of the fungus to establish itself in the gut.” It was also expected that candidalysin, a peptide toxin produced by the fungus, would not support colonization due to its role in triggering inflammatory responses. Surprisingly, the study revealed that candidalysin and two additional proteins, Als3 and Hwp1 (both associated with the hyphal form of the fungus), are essential for colonization and persistence in the gut. Mutant strains lacking these proteins were much less capable of long-term colonization. 

Lead investigator David Corry emphasized that these findings point to fungal hyphal factors as critical for gut colonization. He suggested that targeting these factors could improve efforts to limit gut colonization and reduce the health risks posed by C. albicans.