Non-invasive assessment of barrier integrity and function of the human gut

Abstract

Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease, and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion, including trauma and major surgery. Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease. A variety of tests have been developed to assess intestinal epithelial cell damage, intestinal tight junction status and consequences of intestinal barrier integrity loss, i.e. increased intestinal permeability. This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.

Keywords: Intestinal barrier function; Intestinal integrity; Intestinal permeability; Markers.

Figures

Figure 1

Translocation of compounds from the gut lumen to the circulation via a defective intestinal barrier. A: The intestinal 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 both via the 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 circulation via the 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.