Modelling Candida albicans infection of the human gut using human intestinal organoid cultures

Fungal infections pose a major public health problem, and understanding how infection starts is crucial for developing effective treatments and prevent further disease. In the human gut, fungi form part of the healthy microbiota, but infection occurs when host defences are compromised and the fungus escapes through the intestinal wall into the bloodstream to cause life-threatening infections. Candida albicans is the most prominent human gut fungus and our understanding of how it crosses the gut wall to cause infection is very limited. Complex interactions between the fungus, the gut environment and the gut lining are likely to be involved.

Commonly used infection models rely on the use of experimental animals to shed light on processes relevant to human health. However, this project aims to replace animals and to develop a new culture-based system to understand how gut fungi can invade and infect humans. We will use a new technique called ‘human mini-guts’ to increase our understanding of fungal infection in the gut of humans. This technique is based on human gut tissue which is surgically removed from patients suffering severe intestinal diseases. Excess tissue from surgeries is donated by patients for research at Aberdeen Royal Infirmary. Using these tissue donations we can study the human gut in culture to gain new insights into fungal-gut interactions and the processes that lead to infection and disease. Using this model we will look at how the fungus attaches to the gut lining and penetrates through the gut barrier and how it causes local gut inflammation. We will also study other factors in the gut that could enhance fungal infection. The study is a collaboration between scientists at the Rowett Institute with interest in gut function and the MRC Centre for Medical Mycology with expertise in fungal infections and their treatment. The project will enable us to study human gut function in culture without the use of animals. As a PhD studentship we will also provide extensive training opportunities for a student, and the wider research community, on the importance of alternatives to replace animal testing.