Agnes Meheust, Muriel Derrien, Patrice D. Cani, Freddy J. Troost, Thomas T. MacDonald, Vassilia Theodorou, Jerry M. Wells, Robert-Jan M. Brummer, Annick Mercenier, Willem M. de Vos, Jan Dekker, Clara Lucia Garcia-Rodenas, Arjen Nauta, Animal Sciences, Host-Microbe Interactomics, Wageningen University and Research Center (WUR), School of Medicine and Health, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Centre Daniel Carasso, Danone Nutricia Research, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London (QMUL), University Hospital Maastricht, Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Center (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Metabolism and Nutrition Research Group, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Louvain Drug Research Institute, Université Catholique de Louvain, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Groupe Danone, Laboratory of Microbiology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institute of Nutritional Science, Nestlé Research Center, FrieslandCampina, Wageningen University and Research [Wageningen] (WUR), Maastricht University Medical Centre (MUMC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, UCL - SSS/LDRI - Louvain Drug Research Institute, and Wells, Jerry M.
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.