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Review
. 2017 Mar 1;312(3):G171-G193.
doi: 10.1152/ajpgi.00048.2015. Epub 2016 Dec 1.

VSports注册入口 - Homeostasis of the gut barrier and potential biomarkers

Jerry M Wells  1 , Robert J Brummer  2 , Muriel Derrien  3 , Thomas T MacDonald  4 , Freddy Troost  5 , Patrice D Cani  6 , Vassilia Theodorou  7 , Jan Dekker  8 , Agnes Méheust  9 , Willem M de Vos  10 , Annick Mercenier  11 , Arjen Nauta  12 , Clara L Garcia-Rodenas  11
Affiliations
Review

Homeostasis of the gut barrier and potential biomarkers

"VSports" Jerry M Wells et al. Am J Physiol Gastrointest Liver Physiol. .

Abstract

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 VSports手机版. 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. .

Keywords: antimicrobial peptides; epithelial permeability; gut barrier; microbiota V体育安卓版. .

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Figures (V体育安卓版)

Fig. 1.
Fig. 1.
A: simplified schematic view of the location of the cellular junctions in juxtaposed epithelial cells (EC). Tight junctions (TJs) form the most apical junction and interconnect laterally neighboring cells in the epithelium. TJs allow selective diffusion of fluids, electrolytes, and small molecules through the paracellular space while providing a highly selective barrier for larger molecules, thereby regulating paracellular permeation of ions and other molecules. Adherens junctions are involved in cell-cell adhesion and intracellular signaling. Other basolateral epithelial junctions include desmosomes and gap junctions, which are involved in cell-cell adhesion and intracellular communication, respectively. B: TJs are composed of several types of occludins, junctional adhesion molecule (JAM) proteins, and members of the claudin protein family that influence the charge selectivity of the TJ. These are all transmembrane proteins that form intermolecular and intercellular connections within the paracellular space. All transmembrane junctional proteins interact with intracellular scaffold proteins (such as ZO-1, -2, and -3) that interact with other proteins, including actin in the cytoskeleton.
Fig. 2.
Fig. 2.
Fluorescence microscopy of mucus and microbiota in Carnoy-fixed sections of colon (A) and ileum (B) from mice. Mucin 2 (Muc2) was detected by immunofluorescence using anti-Muc2 and goat-anti-rabbit Alexa Cy3 antibodies (red). Nuclei were visualized using DRAQ5 (blue). Bacteria were identified using fluorescence in situ hybridization and the universal Euprobe 388 (green). C: Alcian blue/periodic acid Schiff-stained colonic tissue (frozen section) from a mouse showing a dark blue firm mucus layer, dark blue-stained goblet cells, and fecal material in the lumen. D: section of ileum (formalin fixed) from a conventional mouse stained with the Crossmon procedure. Arrows indicate segmented filamentous bacteria (SFB), which in contrast to other commensals, are typically found in contact with the epithelium.
Fig. 3.
Fig. 3.
Schematic representation of the protective mechanism of IgA, secretory IgA (sIgA), or secretory component (SC) in the intestinal mucosa. 1: plasma cells in the lamina propria (LP) produce polymeric IgA, which is transported across epithelial cells (a process known as transcytosis) to the lumen by the polymeric Ig receptor (pIgR), where it may interact with antigens of bacteria, viruses, toxins, etc. to exclude them from contact with the epithelium. 2: in the LP, polymeric IgA (pIgA) can bind to immune complexes, including those comprising infectious agents, leading to their removal by removed by transcytosis. 3: pIgR-mediated trafficking of pIgA through epithelial cells can interfere with intracellular viral assembly in the Golgi apparatus. 4: free SC in the lumen has been shown to neutralize pathogen-derived toxins and adehsins. 5: sIgA facilitates uptake of pathogens into IgA-inducing Peyer’s patches and isolated lymphoid compartments and presentation to dendritic cells the subepithelial dome region. Recognition of sIgA by dendritic cells is reported to inhibit IL-12 cytokine secretion, leading to induction of helper T cell 2 (Th2) or regulatory T cell (Treg) responses.
Fig. 4.
Fig. 4.
Schematic model of gut-brain signaling representing five components, with a central role of host-microbe interaction and intestinal barrier function (for detailed description, see text).
See this image and copyright information in PMC

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