Host-microbiota interactions in inflammatory bowel disease

Host-microbiota interactions have been linked to a growing list of diseases such as inflammatory bowel diseases (IBD), obesity, diabetes, etc.. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, consisting of two predominant subtypes, ulcerative colitis (UC) and Crohn's disease (CD). The exact mechanism by which this disease arises is unknown, however it is believed to emanate through a combination of an exaggerated immune response in a genetically susceptible host, triggered by environmental factors. We are interested in studying the molecular changes that occurs in host and microbiota during gut dysbiosis and to develop screening techniques for microbiome with a particular focus on new onset IBD in Children.

Briefly, biopsies and aspirates from the mucosal-luminal interface from a large-cohort (>100) of new-onset pediatric IBD patients were obtained at the time of diagnostic endoscopy. This inception cohort includes non-IBD control, UC and CD patients with mild to severe IBD activity as determined through validated clinical disease activity scores. Within the intestinal aspirate samples, the presence of both human and bacterial proteins can be detected.

First, we will report on our efforts at combining different omics approaches to reveal changes in pathways/networks and bacterial compositions indicating an altered crosstalk. In particular, we will present the proteomic analysis of the host proteome which identifies new biomarkers of the disease and reveals insight on potential mechanisms of host responses to the disease. We will also present results from our omics analysis of the changes that occur in the gut microbiome.

An important challenge when studying the microbiome is the lack of assays to rapidly assess microbiome responses to different challenges. We have developed an approach called rapid assay for individual's microbiome (called RapidAIM) to perform ex vivo assays to study the effects of drugs on the human gut microbiome. We will present results on ex vivo response of individual gut microbiome to challenges with different compounds including prebiotics and drugs.