Intestinal nutrient sensing and signalling in gut- and metabolic health

Intestinal nutrient sensing and signalling in gut- and metabolic health

This research theme within the Chair of Nutritional Biology investigates nutrient sensing mechanisms that trigger signalling of gut hormones and neurotransmitters to convey information about energy status and gastrointestinal health to other organs and tissues, such as brain, pancreas, adipose tissue and the immune system. Our goal is to understand how dietary- and microbial-derived metabolites interact with intestinal nutrient sensing mechanisms in order to optimize food-intake, intestinal physiology and overall health.

Gut peptide hormones as well as neurotransmitters play essential roles in gut physiology and inter-organ communication. Disturbed signalling contributes to metabolic diseases, as present in the obese and ageing population, and often plays a role in intestinal disorders. In order to understand and potentially modulate gut signalling we aim to unravel interaction of nutrients, dietary- and microbial metabolites from foods with nutrient sensing chemoreceptors. This includes components without nutritional value such as additives or bio-actives derived from plants.

Research topics

Gut hormone signalling  in metabolic health

One of the largest endocrine tissues in the body is formed by the enteroendocrine cells of the gastrointestinal tract. Different enteroendocrine cells release a diverse range of hormones each exhibiting specific functionalities. Among these, probably the best studied peptide hormone is glucagon like peptide 1 (GLP-1), which is momentarily a key target in the treatment of Type 2 Diabetes (T2D). GLP-1, which is predominantly produced in the gastrointestinal tract, controls energy homeostasis by regulating pancreatic insulin release, gastric emptying and eating behaviour. Other gut hormones including cholecystokinin (CCK) and plasma peptide YY (PYY) are involved in satiety and food intake. How dietary metabolites can influence intestinal peptide hormone signalling via activation of nutrient sensing receptors and impact metabolic health and obesity in the ageing population is one of our main interests.

Bitter taste receptors in GLP-1 signalling  and Type 2 Diabetes

Here, we study the roles of intestinal expressed nutrient sensing bitter taste receptors on the release of GLP-1. Nutrient-sensing G-protein coupled receptors (GPCRs) expressed on enteroendocrine cells recognise bitter components, trigger peptide hormone release and can impact insulin sensitivity and consequently the development of Type 2 Diabetes (T2D). Although bitter taste is thought to be evolutionary linked to toxicity, more than half of the known bitter compounds are non-toxic and valued and beneficial ingredients of our diet. We investigate bitter vegetables, like bitter gourd, but also the effects of bitter tasting constituents of our diet, such as steviol glycosides and certain flavonoids.

Sensing and signalling via odorant chemosensors

Interestingly, the presence of odorant receptors is not limited to the oro-nasal area. Instead, they have been found in various other organs and tissues, including the gastro-intestinal tract. How odorant chemosensors can play a role in metabolic- and gut health is a new and exciting research area. The odorant GPCRs form the largest subgroup within the GPCR superfamily. In the gut, odorant receptors are expressed on enteroendocrine cells, where they modulate signalling of serotonin, GLP-1 and PYY and respond to dietary components and microbial metabolites including short chain-, medium- and branched chain fatty acids derived from complex carbohydrates and proteins. Besides, they detect metabolites present in fruits, vegetables and herbs. Our goal is to further unravel their functionality in the gastrointestinal tract and other metabolic active tissues in relation to nutrition.   

Fatty acid conjugates with immune-modulatory and anti-oxidant properties

Fatty acid amides are important signalling lipid molecules present throughout the body. We investigate the group of n-3-PUFA- and oleic acid-derived fatty acid amides as they have immune-modulatory, anti-oxidant and satiety-inducing properties. Their endogenous roles are not only relevant for gut health but also in relation to gut-brain communication and obesity-associated metabolic disorders. Of particular interest is the function and potential of fatty acid conjugates with serotonin, present in gut. These have been found to interact with the immune system, the intestinal serotonin pathway and their formation can be modulated by the diet.

Effects of natural antimicrobials on gut health

Within this project we study effects of newly discovered natural antimicrobials on intestinal health. There is an urgent need for new natural antimicrobials as alternatives for synthetic compounds to used for example as preservatives in (food) products. However, it is not known how these ‘novel’ antimicrobials can affect (intestinal) health. In particular we study prenylated phenolic compounds derived from plant roots, which have been shown to act as potent antimicrobials against potential pathogens relevant for foods as well as for oral and general health.