Gut barrier integrity as the defining factor for obesity-associated systemic inflammation - A clinical proof-of-concept study

Project synopsis

Obesity and obesity-related diseases are intricately linked to a chronic state of systemic low-grade inflammation. Understanding the clinical and mechanistic links between obesity and the development of systemic inflammation is crucial for developing effective treatments against obesity-related complications. Obesity and nutritional status impact the intestinal immune system and gut barrier integrity, with an obesity-related increase in gut barrier permeability as the potential driver of systemic inflammation. Using 5-aminosalicylic acid (5-ASA), an anti-inflammatory drug working locally in the gut, we aim to evaluate the role of gut barrier integrity in systemic inflammation. In a placebo-controlled clinical study in patients living with obesity, we will assess the impact of 5-ASA on, the primary endpoint, high sensitivity C-reactive protein (hsCRP) complimented by a fundamental and translational approach involving biomarker analysis and mechanistic investigations of barrier integrity.

Framework 

The clinical research environment at Center for Clinical Metabolic Research (CCMR), headed by Asger B. Lund, offers an opportunity to conduct clinical studies in a research setting with significant experience in physiological and pathophysiological clinical research within human metabolism. Projects at CCMR focus on the role of the gastrointestinal tract and its hormones and on metabolic diseases like diabetes, obesity, and MASLD. An established collaboration between Benjamin A. H. Jensen and CCMR combines fundamental, translational, and clinical research approaches with a focus on obesity-related gut barrier (dys)function and systemic low-grade inflammation. Fundamental and translational knowledge on gut barrier function and compartmentalised immunology provided by the Jensen group and an industrial view on early discoveries combined with clinical experimental medicine expertise provided by Filip K. Knop add to the generation of impactful and translatable research.

Ideal fellow candidate

  • MD-PhD
  • Certain experience with conducting larger clinical studies
  • Certain experience with translational research
  • A wish and ability to engage in a clinical study with a focus on mechanistic explorations
  • Fluent in Danish

Mentor team

Basic mentor: Benjamin A. H. Jensen, Associate Professor, Nutritional Immunology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Clinical mentor 1: Asger Bach Lund, MD, Associate Professor, Director of Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

Life science industry mentor: Filip Krag Knop, MD, Senior Medical Officer for Diabetes & Obesity, Corporate Vice President, Novo Nordisk, Professor of Endocrinology, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Contact 

If you are interested in the project, please contact Associate Professor Asger B. Lund on Asger.Lund.01@regionh.dk. 

If it is a match, you and the mentor team will together apply for a fellowship by the deadline of 16 February 2025.