Lab of Gastroenterology & Hepatology

Main research topics:

The main study topics of the division of Gastroenterology and Hepatology are the neuromuscular transmission in the gastrointestinal tract, visceral hypersensitivity and afferent signalling in physiological and pathophysiological inflammatory conditions; the mechanisms of motility disorders in postoperative and septic ileus; the therapeutic potential of treatment of colitis with worms and worm proteins; the mechanisms of portal hypertension and the intrahepatic resistance and its determinants in severe non-alcoholic fatty liver disease (NAFLD).

IBD and IBS: visceral hypersensitivity

Two of the most important and frequent pathologies in the field of gastroenterology are irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. Visceral hypersensitivity, disturbed intestinal motor function and psychological aspects have been identified as important contributors. Treatment is clinically challenging.

In our research lab, we employ different animal models of acute and chronic colitis to study the mechanisms of colitis-induced visceral hypersensitivity, in the acute phase of colitis and in the remission phase when inflammation has subsided while gut abnormalities continue to exist. In rat and mouse TNBS colitis and ileitis models, visceral sensitivity disturbances and the role of several mediators and receptors involved (histamine, vanilloids, cytokines, ...) were investigated. This research resulted in two PhDs between 2008-2013 (Heiko De Schepper and Wim Vermeulen) and a PhD  defended in September 2014 (Annemie Deiteren).

Besides the interaction between the bowel and the bladder is investigated in a translational setting, resulting in a PhD in defended  July 2014 (Michel Wyndaele).

 

IBD and immunological-mediated therapies

In a TNBS and a chronic colitis transfer model we investigate the therapeutic potential and the immunological pathways involved in helminth or helminth-derived therapy which interfere with the local colonic cytokine equilibrium. We specifically focus on the role of T-cells and dendritic cells (DC) and their inflammatory cytokines such as TNFα and IL17. This research resulted in one PhD between 2008-2013 (Nathalie Ruyssers) and a PhD  defended in September 2014 (Marthe Heylen) and a novel PhD project starting up in September 2014.

 

Sepsis and septic ileus

Sepsis is the leading cause of death in critically ill patients but clinical sepsis trials have a long history of failure. A novel treatment approach is based on inclusion of patients taking into account the immune profile of the individual patient and the particular phase of sepsis they are in.

Our research focuses on the gastrointestinal (GI) tract as an important initiator of sepsis. Using different animal models (LPS and CLP) and samples from septic patients, we study the immune response in the GI wall in comparison with the systemic immune reaction using flow cytometry, molecular biology, immunoassays and immunohistochemistry. Our aim is to find tissue-specific and systemic biomarkers enabling a better inclusion strategy for future clinical trials for the treatment of sepsis. This project is part of an ongoing PhD (Sara Nullens).

 

Steatosis and portal hypertension – role of autophagy and ER stress

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as an important source of liver-related morbidity and mortality, taking epidemic proportions because of its intimate link with the metabolic syndrome and its features. Steatosis can be accompanied by signs of inflammation and hepatocellular damage, leading to non-alcoholic steatohepatitis (NASH).

In a rat model of steatosis and steatohepatitis, we previously demonstrated that a methionine–choline-deficient (MCD) diet rapidly induces steatosis and at a later stage also signs of inflammation and oxidative stress. In this rat model of severe NAFLD, we study the mechanisms of portal hypertension in relation to the severity of steatosis. Our research focuses on the mechanisms of intrahepatic resistance and its determinants in experimental NAFLD and the underlying immunological changes of the innate and adaptive immune system. More recently we also started to study the role of autophagy and ER stress in this mechanisms as autophagy plays a major role in the lipid metabolism and lipid accumulation.

This research resulted in two PhDs between 2008-2013 (Sven Francque and Luisa Vonghia, University of Bari, Italy) and an ongoing PhD (Wilhelmus Kwanten).