Address Amsterdam UMC
Department of Gastroenterology and Hepatology
Tytgat Institute for Liver and Intestinal Research
1105 BK Amsterdam
Caroline: +31 20 566 8156 Secretariat (Elsa): +31 20 566 5948
Irritable Bowel Syndrome
IBS is a functional bowel disorder characterized by abdominal pain or discomfort associated with changes in bowel habit. Our research focus is on the role of mast cells and the gut micro-and mycobiome in abdominal pain, and treatment possibilities thereof.
Translated targets – mast cells and histamine-1 receptors
Stress is an important trigger for abdominal pain complaints in IBS. Using a pre-clinical model, we showed that stress-induced mast cell degranulation and subsequent histamine release leads to activation of the histamine-1 receptor (H1R) and hypersensitivity to colorectal distension. In this model, we showed that a mast cell stabilizer and ebastine, a H1R antagonist indicated for allergic rhinitis, both reversed post stress visceral hypersensitivity. In Amsterdam and Leuven, this knowledge was translated into a successful clinical trials were ketotifen and ebastine reduced abdominal pain in IBS patients.
Current focus – the gut mycobiome (yeast)
We now aim to identify molecular triggers important for mast cell degranulation. Although the stress hormone CRF was implicated, our results indicated that CRF is relevant as a first hit only: continued post stress degranulation depends on other triggers. Using fungicide treatment and fecal mycobiome transfers in IBS-like rats, we showed the relevance of an altered gut mycobiome. Since we also observed mycobiome dysbiosis in IBS patients, we now address treatment options that favorably change the gut mycobiome or interfere with yeast-immune interaction. In a collaborative study with Dr Willmar Schwabe Pharmaceuticals, a combination of essential oils changed the mycobiome composition and reversed visceral hypersensitivity. In another study we aimed at repurposing an existing drug. We showed that miltefosine, which is approved for treatment of visceral leishmaniasis, is also a mycobiome modulator capable of reversing visceral hypersensitivity.
Because part of the Inflammatory Bowel Disease (IBD)-patients in remission also suffers from abdominal pain complaints, we recently expanded our investigations and now address IBS as well as IBD-remission.