This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 956851.

Prof. Tim Vanuytsel, MD PhD

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), KU Leuven, Leuven, Belgium

Division of Gastroenterology and Hepatology, University Hospital Leuven, Leuven, Belgium

Leuven Intestinal Failure and Transplantation Center, University Hospital Leuven, Leuven, Belgium.

Prof. Tim Vanuytsel graduated summa cum laude in 2007 from Leuven University Medical School. He obtained a PhD degree in biomedical sciences in 2014 with a thesis on the role and mechanisms of intestinal permeability in functional gastrointestinal disorders. During his PhD training, he worked as a researcher in the lab of Prof. Terez Shea-Donohue at the University of Maryland, Baltimore (USA) in 2011.

Prof. Vanuytsel currently holds a position as a consultant gastroenterologist in Leuven University Hospitals with a clinical focus on intestinal failure, clinical nutrition and functional gastrointestinal disorders. He is the co-founder and medical director of the Leuven Intestinal Failure and Transplantation center (LIFT), which is the largest intestinal failure center and the only small bowel and multivisceral transplant center in Belgium.

Tim Vanuytsel is an assistant professor at the University of Leuven and his research interests include the pathophysiology and treatment of functional gastrointestinal disorders and intestinal failure and transplantation. In a close collaboration with Prof. Patrick Augustijns (Drug Delivery and Disposition, KULeuven) he investigates drug disposition through in vivo sampling with a focus on colonic targeted drugs. He has published >105 original research articles and reviews in international peer-reviewed journals on both clinical and basic science aspects of gastroenterology. He is the (co-)supervisor of 15 PhD students and 2 postdoctoral fellows. He is the editor in chief of Acta Gastroenterologica Belgica, associate editor of the GI section of Current Opinion in Pharmacology and member of the editorial board of Neurogastroenterology and Motility.



Optimizing colonic sampling and its application to drug disposition studies

Documentation regarding the sampling of colonic contents and the gastrointestinal behaviour of low solubility compounds at the level of the colon is limited. To reliably sample colonic content, we developed an adequate colon preparation procedure and sampling technique. To ensure that the physiological state of the proximal colon remains undisturbed, we opted to administer rectal enemas after a three day low fiber diet. By varying the frequency and volume of the enemas, we observed that a one-time enema of 250 mL of water appeared sufficient to cleanse the left hemicolon while avoiding spill over to the right hemicolon where then physiologically relevant samples could be taken. We evaluated several approaches to sample colonic content: (i) collection with an endoscopic foreign body retrieval device (ii) aspiration with a Faucher catheter or a weighted duodenal tube which were attached during the colonoscopy to the mucosa of the ascending colon with hemostatic clips, (iii) sampling as much caecal contents as possible through the suction channel of the colonoscope. 

This latter option turned out to be the most reliable way to collect the contents from the proximal colon, although the viscosity of the colonic contents limits this technique to one sample per colonoscopy. This procedure was applied in two clinical studies in which we aimed to distinguish plasma- from gut-driven tissue accumulation after oral intake of Celebrex® (celecoxib) or Arthrocine® (sulindac). More specifically, the clinical studies were designed for the drug’s systemic Tmax to drop in-between two colonoscopies with serial caecal biopsies and aspiration of colonic contents at the end of each procedure. Plasma levels are expected to increase in this first phase (between 1 and 2.5 h post drug intake) and drive caecal tissue accumulation. In the second phase (between 6 and 7.5 h post drug intake), plasma levels are expected to decrease. By analysing the profile of tissue drug levels in combination with the plasma and luminal levels, plasma-driven vs. gut-driven accumulation could be distinguished.