Nutrition and intestinal biology

This topic investigates how nutrient sensing mechanisms are activated by nutrients, dietary- and microbial metabolites in the gastrointestinal tract. Nutrient sensing triggers the release of gut hormones, such as the well-known glucagon-like-peptide-1 (GLP-1). Gut peptide hormones play essential roles in human physiology as they communicate with other organs such as the brain and pancreas, thereby influencing brain functioning, insulin sensitivity, protein digestion and food intake. Disturbed signalling contributes to diseases, such as those found in the ageing and obese population. To understand and influence intestinal signalling by the different gut hormones (e.g. GLP-1, GIP, somatostatin, CCK, PYY), we aim to unravel interactions of food metabolites with G-protein coupled chemoreceptors, such as sweet, bitter, fatty acid, and olfactory receptors. We developed an innovative 3D human apical-out organoid model optimized for nutritional studies and perform (human) intervention studies. Knowledge will lead to valuable insights into the impact of nutrition on gut physiology and health.

Our diet is a complex mixture of macromolecules. After being digested, nutrients are absorbed by absorptive cells, and gut microbes utilize undigested food to keep them alive and generate microbial metabolites. The gut microbiome produces a diverse metabolite repertoire by breaking down dietary products and endogenously synthesizing essential cofactors. Only a limited number of microbial metabolites derived from carbohydrates, lipids, and proteins have been reported and demonstrated to influence intestinal health through various signaling pathways. Indeed, each microbial genome encodes the ability to generate hundreds, if not thousands, of molecules. However, many microbial metabolites have not yet been characterized, and their biological role remains unexplored. We aim to expand our knowledge and go beyond the state-of-the-art on food-gut microbiome interactions, creating a comprehensive spatiotemporal atlas (microbial and metabolite data) from the SI and colon using omics and computational tools to untangle the mechanisms.

The upper and lower intestines react to dietary components and byproducts generated during digestion and microbial fermentation. These responses are crucial for maintaining gut health, regulating nutrient absorption, and influencing overall metabolic processes. In this research line, we investigate microbial metabolite - gut epithelium interactions in vitro using 2D intestinal organoids monolayers in combination with omics approaches. With this multidisciplinary approach, we currently investigate how algae-derived lipids, protein-related metabolites (plant and animal origins), flavan-3-ol catabolites, alkylresorcinols, and advanced-glycated end products interact with intestinal epithelial cells. We aim to elucidate the biological mechanisms by which microbial metabolites influence intestinal epithelial cells and promote barrier functionality.

Intestinal barrier dysfunction, characterized by increased gut permeability, plays a crucial role in systemic inflammation and aging-related pathologies. Our research has developed novel methodologies to assess intestinal permeability, including a peptide (AraH6)-based approach in humans and a unique human air-liquid interface trans-well gut-organoid system. We have identified mitochondrial dysfunction as a key factor contributing to impaired gut barrier integrity. Ongoing research aims to further delineate the interplay between intestinal barrier dysfunction, immune aging, and systemic inflammation, utilizing advanced methods to detect senescence of the innate immune system both in vitro and in vivo. This emerging field of study is redefining our understanding of the interconnected pathophysiological changes that occur with aging and chronic diseases.

This research theme addresses the fate of dietary proteins in the body with a focus on digestion, absorption in the gastrointestinal tract. This will gain insights that will aid the selection of protein sources for the human diet, particularly related to the transition towards eating more plant-based proteins, as recommended by the Dutch Health Council. The selection is high quality protein sources isa matter that is particularly important for vulnerable populations (e.g. older adults) that are at risk for protein malnutrition. The fate of proteins that are not digested or absorbed is also of relevance. These undigested and unabsorbed proteins, peptides and amino acids may be fermented by the gut microbiome, leading to metabolites that influence (gut) health. The work carried out in this theme benefits from the close collaboration between the division of Human Nutrition and the department of Animal Nutrition.

Fatty acid amides are important signaling lipid molecules throughout the body. We investigate the role, effects and kinetics of n-3-PUFA- and oleic acid-derived fatty acid amides in relation to disorders with an inflammatory component. Of particular interest is also the function of fatty acid conjugates with serotonin. They possess anti-inflammatory and anti-oxidant properties and their levels can be influenced by the diet. This raises perspectives not only from a nutritional point of view but also for the gut-brain axis.