Interaction between intestinal fungi and bacteria in the regulation of gut permeability and inflammation

Growing evidence suggest that increased gut permeability and bacterial dysbiosis contribute to several human diseases including inflammatory bowel diseases (IBDs). Therefore. it has been suggested that reconstruction or modulation of the intestinal bacterial microbiome represents a novel and well-perceived treatment option. Previous studies have been largely focused on bacteria. although accumulating evidence indicates that intestinal fungi are also associated with inflammation in the gut. However. the role of intestinal fungi and their interactions with bacteria in the regulation of the gut permeability and mucosal immune responses remain largely unknown. Therefore. the goal of this project is to define the role of intestinal fungi and their interactions with bacteria in gut permeability and host immune responses. 
 Our preliminary data of bacterial and fungal microbiome analysis in patients with Crohn???s disease (n=35). ulcerative colitis (n=98). and irritable bowel syndrome (n=92) along with healthy individuals (n=112) revealed that the presence of two fungal species. Candida albicans and Candida tropicalis is inversely correlated with three bacterial species Lactobacillus ruminis. Bifidobacterium adolescentis. and Faecalibacterium prausnitzii. We further found that the inter-kingdom interactions do exist in vitro. as L. ruminis inhibited growth of C. albicans and C. tropicalis. In addition. C. albicans can increase permeability of the epithelial cell monolayers and this activity is blocked by L. ruminis.As increased permeability of the intestinal epithelial barrier promotes inflammation it is therefore important to understand how C. albicans induces ???leaky gut???. Therefore. in this pilot proposal we will elucidate how C. albicans increases gut permeability and promotes inflammation (Aim 1) and test the efficacy of L. ruminis. B. adolescentis. and F. prausnitzii probiotic bacteria to control C. albicans (Aim 2) in murine model.