The colon microcosm: a novel in vitro model to study Candida albicans colonisation of the human colon

Abstract

Candida albicans colonises the gastro-intestinal (GI) tract of over 60% of the population. In severely ill or immune compromised patients, this fungus can escape the gut, disseminate through the body and cause systemic disease. Most research in the field has focused on defining traits that contribute directly to virulence; there are comparatively few studies which have addressed how C. albicans colonises and persists in the gut. Furthermore, such studies have typically been performed mouse models devoid of resident GI bacteria, completely neglecting the major impact of the local microbiota on GI colonisation. How, then, does C. albicans persist in the GI tract in the presence of the normal gut microbiota? To address this question, a novel in vitro two-phase anaerobic fermentation system that simulates the human colon microenvironment has been developed. This “colon microcosm” supports the growth of human faecal microbiota in liquid anaerobic colon medium (phase 1) and C. albicans growth on agar plugs which are added to the medium to mimic the epithelial surface (phase 2). The impact of C. albicans upon the faecal microbiota is monitored by examining the planktonic phase (phase 1), whilst the effect of the microbiota on the growth of C. albicans is monitored after extracting C. albicans cells from the agar plugs (phase 2). The results of assays carried out to validate the model will be presented, as will data from pilot studies which illustrate the potentially exploitable impact of the human GI microbiota from healthy individuals on C. albicans growth.