In this review, the currently available methods aiming to assess either human intestinal barrier integrity or intestinal barrier function will be discussed. intestinal barrier integrity and function. Keywords:Intestinal integrity, Intestinal barrier function, Intestinal Zaltidine permeability, Markers == INTRODUCTION == The gastrointestinal tract is the most extended surface acting as a barrier between external environment and internal milieu. The host integrity is maintained by effective monitoring of the mucosal surface and sealing the host interior against potentially harmful compounds such as bacteria, toxins and antigens. This function of the gastrointestinal tract is referred to as intestinal barrier function. The intestinal epithelial barrier function consists of multiple defense mechanisms which can basically be subdivided into a physical and an immunological barrier[1-3]. The physical intestinal barrier is composed of a lining of epithelial cells, connected by tight junctions (Figure1A). These adhesion structures serve as a fence sealing the paracellular pathway, thereby preventing exposure of the internal milieu to potentially harmful intraluminal microbiota and microbial products[4]. Tight junctions are anchored in the cell via the filamentous actin (F-actin) cytoskeleton[5]. Zonula occludens proteins (ZO-1, ZO-2 and ZO-3) are important intracellular tight junction proteins, linking the cell cytoskeleton to the transmembrane tight junction proteins: claudins, occluden and junctional adhesion molecules (JAM). Whereas occludin and JAM have a regulatory role, claudins are transmembrane proteins mainly responsible for the intestinal barrier function[6]. The physical barrier is reinforced by the presence of a mucus layer, produced and secreted by goblet cells[7]. The immune barrier is formed by specialized epithelial cells, the Paneth cells, located in the crypts of the small intestine, which can actively sense bacterial presence and prevent colonization of the crypts by releasing antimicrobial proteins including lysozyme and defensins[8,9]. Furthermore, lamina propria immune cells actively participate as immune sensors of microbial pathogens and commensal organisms. Bacterial recognition is dependent Zaltidine on transmembrane and intracellular pattern recognition receptors, including the structurally homologous Toll-like receptor (TLR) Zaltidine and NOD-like receptor Zaltidine (NLR) family. Ligation to these bacterial receptors stimulates central signaling cascades (NF-B, AKT/phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways), resulting in an immunological response[10-13]. == Figure 1. == Translocation of compounds from the gut lumen to the circulationviaa defective intestinal barrier. A: The intestinal Zaltidine epithelial barrier is composed of a lining of enterocytes (1) tightly connected by tight junctions (2) to prevent the translocation of intraluminal compounds to the circulation. Claudins (2a), important transmembrane tight junction proteins responsible for sealing the paracellular space, are tightly connected to intracellular protein ZO-1 (2b), which is anchored to the cell cytoskeleton (2c); B: Differential sugar absorption test: Lactulose (L), a disaccharide, is only able to traverse the paracellular pathway in case of compromised intestinal barrier function. Mannitol (M) is a monosaccharide which can cross the intestinal barrier bothviathe trans- and paracellular pathway, thereby serving as an internal control to correct for confounders as gastric emptying, mucosal perfusion and renal function; C: Endotoxin core antibody (EndoCAb) (1) is consumed when endotoxin (2), derived from intraluminal Gram-negative bacteria (3), translocates from the intestinal lumen to the circulationviathe defective intestinal barrier; D: D-Lactate (1) is a fermenting product from intestinal bacteria (2). In case of barrier function loss, D-Lactate can be detected in plasma. Disturbed intestinal Rabbit Polyclonal to AIG1 barrier function is considered a key factor in the development and/or progression of intestinal inflammation, and is therefore thought to play a role in both the pathogenesis and the perpetuation of various intestinal diseases including inflammatory bowel disease (IBD) and celiac disease[2,3]. Impaired intestinal barrier function has also been assumed to play a role in the development of sepsis and multiple organ failure (MOF) in patients with decreased gut perfusion following major surgery, trauma or shock[14,15]. Recently the occurrence of splanchnic hypoperfusion during major surgery was reported to result in intestinal ischemia and intestinal barrier integrity loss[16], which could in turn facilitate translocation of bacterial products from the intestinal lumen to the.