Functionally decoding the contribution of human host-fungal interactions to the pathogenesis of IBD.

Our gut microbiome has a strong influence on a variety of diseases, including Inflammatory Bowel Disease (IBD). Fungi form an integral part the human gut microbiome, and studies in mice showed that fungi may have a substantial influence on inflammation and IBD development, while antibody responses against fungi constitute important clinical IBD diagnostic tools. However, the functional roles of fungi in modulating IBD, and whether they can be harnessed towards new treatments, remain elusive to date. In this study, we plan to uncover the role of fungi in IBD by taking biopsy samples of the gastrointestinal tract from IBD patients. From the biopsies, we plan to grow mini-guts, called organoids, in petri dishes. We have previously shown that it is possible to use these organoids cultured with microbes to study the interactions between bacteria and the gut cells. Thus, using IBD patient-derived gut organoids and specific IBD-relevant fungi, we will be able to identify mechanisms of the interactions between the diseased gut cells and the fungi. Interesting fungal candidates will be further validated in IBD-like mouse models. This combination of different approaches will allow us to better understand the influence of fungi on IBD progression and develop new intervention strategies for treating IBD.