HUMAN INTESTINAL BARRIER FUNCTION IN HEALTH AND DISEASE
Wells J. M.1, Brummer R. J.2, Derrien M.3, MacDonald T. T.4, Troost F.5, Cani P. D.6, Theodorou V.7, Dekker J.1, Méheust A.8, de Vos W. M.9, Mercenier A.10, Nauta A.11, Garcia-Rodenas C. L.10
1 Host-Microbe Interactomics Group, Animal Sciences, Wageningen UR, The Netherlands;
2 Nutrition-Gut-Brain Interactions Research Centre, School of Medicine and Health, Örebro University, Sweden;
3 Centre Daniel Carasso, Danone Research, 91767 Palaiseau, France;
4 Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, U.K.;
5 Division of Gastroenterology-Hepatology, Department of Internal Medicine, University Hospital Maastricht, Maastricht University Medical Centre, The Netherlands;
6 Louvain Drug Research Institute, WELBIO, Metabolism and Nutrition Research Group, Université Catholique de Louvain, Brussels, Belgium;
7 Neuro-Gastroenterology and Nutrition Group, INRA UMR1331 Toxalim Toulouse, France;
8 The International Life Sciences Institute, European Branch, Brussels, Belgium;
9 Laboratory of Microbiology, Wageningen UR, Building 316, Dreijenplein
10 6703 HB Wageningen, The Netherlands; 10. Nutrition & Health Research, Nestlé Research Center, Lausanne, Switzerland;
11 FrieslandCampina, Amersfoort, The Netherlands.
This introductory lecture will give an overview of the factors maintaining intestinal barrier function and the role of a ‘leaky gut’ in the pathophysiology of a variety of gastrointestinal disorders. The gut barrier plays a crucial role by spatially compartmentalising bacteria to the lumen through the production of secreted mucus and is fortified by the production of sIgA and antimicrobial peptides and Reg3 family proteins. With exception of sIgA the expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialised adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine.
Increased permeability of the intestinal epithelium is now recognised as having a role in the pathophysiology of a variety of gastrointestinal disorders. Deterioration of
the intestinal barrier function may lead to increased and prolonged mucosal immune activation and consequently to increased afferent sensory signalling and abdominal complaints. In turn, neuronal mechanisms affect the intestinal barrier partly by activation of the HPA-axis and both mast cell-dependent as well as mast cell- independent mechanisms. Aging significantly increases the vulnerability to gastrointestinal disorders but there are few studies investigating the key factors in aging that affect the GI tract. The age-associated changes in barrier function will also be presented and the impact this could have on vulnerability to gastrointestinal disorders, the systemic immune system and organs.
Nutrition and microbe-gut interactions can have a substantial and clinically relevant impact on the development of the immune system and intestinal barrier function with consequences for the resistance to pathogens, development of gut inflammation, and abdominal complaints. This has major implications for the prevention and therapy of a variety of ‘modern’ diseases called ‘immune mediated disorders of affluence’, such as IBS, IBD, and other non-intestinal disorders, such as allergy and type-1 diabetes, which have all dramatically increased in incidences over the past five decades. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases but for many markers there is still a need for standardization, establishment of normal ranges and their predictive values in the general population. Ultimately such markers and assays could be used to assess associations between particular nutritional traits and gut barrier function or experimentally assess the impact of a specific nutritional intervention.
Keywords: Intestinal Barrier Function, Gastrointestinal disorders, Mucosal immune activation, Age-associated changes, Probiotics
Wells J. M., et al. (2016). Human intestinal barrier function in health and disease. Conference Proceedings of IPC2016. Paper presented at the International Scientific Conference on Probiotics and Prebiotics, Budapest (p. 80.). IPC2016