Novel treatment strategies for intestinal injury: the combination of peptides and non-peptide drugs at the dynamic intestinal barrier.

The role of the intestinal mucosa is to form a selective barrier between the luminal contents and the underlying tissue and the systemic circulation.

It  restricts passage of potentially harmful intestinal constituents such as microbiota and toxins, while allowing absorption of water, nutrients and ions.

Intestinal barrier homeostasis is disrupted through tight junction protein dysregulation caused by exposure to bacterial toxins, cytotoxic agents, radiotherapy, and pro-inflammatory cytokines. It can also be affected by intestinal autoimmune disease such as Celiac disease and intestinal ischemia.

The rapid proliferation of intestinal epithelial cells, together with the complex interaction with the gut microbiota, makes the gastrointestinal tract particularly vulnerable for chemotherapeutics.

An inability to rapidly repair epithelial barrier function is detrimental to the cancer patient, as it can result in sepsis and multiple organ failure.

Understanding pathophysiological factors that regulate injured intestinal epithelium is crucial for developing new drug combinations.

This multidisciplinary project will translate the preclinical results  to clinic in a close collaboration between basic and clinical science.

It will conduct quantitative pharmacological system analysis of all in vivo data from biological fluids and intestinal tissues.

It is expected to provide an improved biochemical understanding of the drug actions when the  intestine has been compromised