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Am J Physiol Gastrointest Liver Physiol. 2017 Mar 1;312(3):G171-G193. doi: 10.1152/ajpgi.00048.2015. Epub 2016 Dec 1.

Homeostasis of the gut barrier and potential biomarkers.

Author information

Host-Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands;
Nutrition-Gut-Brain Interactions Research Centre, School of Medicine and Health, Örebro University, Örebro, Sweden.
Centre Daniel Carasso, Danone Research, Palaiseau, France.
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, United Kingdom.
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University Hospital Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life Sciences and BIOtechnology), Metabolism and Nutrition Research Group, Université Catholique de Louvain, Brussels, Belgium.
Neuro-Gastroenterology and Nutrition Group, Institut National de la Recherche Agronomique, Toulouse, France.
Host-Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Danone, Paris, France.
Laboratory of Microbiology, Wageningen UR, Wageningen, The Netherlands.
Institute of Nutritional Science, Nestlé Research Center, Lausanne, Switzerland; and.
FrieslandCampina, Amersfoort, The Netherlands.


The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized 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. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.


antimicrobial peptides; epithelial permeability; gut barrier; microbiota

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