The effect of faecal supernatants from irritable bowel syndrome patients on enteric neurons - with a focus on proteases.

• Applicant: Dr. Anita Annahazi, Ph.D.
• Subject Area: Gastroenterology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459480507

The pathogenesis of irritable bowel syndrome (IBS), a chronic, functional gastrointestinal disorder is very complex and not completely understood. Besides the role of central components within the brain-gut axis, recent evidences underline the importance of peripheral factors, such as luminal proteases in the symptom development of the disease. Previous studies have demonstrated an elevated serine-protease and cysteine-protease activity in stool of IBS patients with predominant diarrhoea (IBS-D) or with predominant constipation (IBS-C), respectively. The faecal supernatants with increased protease activities were shown to cause visceral hypersensitivity in an animal model. Furthermore, the faecal cysteine-protease activity correlated with the abdominal pain in IBS-C patients. The enteric nervous system (ENS) is also involved in the pathology of IBS. Nevertheless, the effect of faecal proteases on the ENS has never been studied.Based on this background, the major aim of the present project is to explore the effect of faecal supernatants from IBS-D, IBS-C and IBS-M (IBS with mixed stool pattern) patients on the ENS, compared to supernatants from healthy controls. This goal will be achieved using voltage sensitive dye imaging on guinea pig submucous neurons. In addition, specific inhibitors and receptor blockers will be used to clarify the role of proteases in this effect. As a last step, proteome analysis for human proteins will be performed to compare the protein pattern of faecal supernatants from IBS patients and healthy individuals. The results of the project may provide new knowledge on the pathogenesis of IBS and identify novel potential biomarkers for the non-invasive diagnosis of the disease.

• DFG Programme: Research Grants