Non-invasive markers of gut wall integrity in health and disease

The intestinal mucosa is responsible for the absorption of nutrients from the lumen and for the separation of the potentially toxic luminal content(external environment) from the host(internal environment).Disruption of this delicate balance at the mucosal interface is the basis for numerous(intestinal) diseases.Experimental animal studies have shown that gut wall integrity loss is involved in the development of various inflammatory syndromes,including post-operative or post-traumatic systemic inflammatory response syndrome,sepsis,and multiple organ failure.Assessment of gut wall integrity in clinical practice is still a challenge,as it is difficult to evaluate the condition of the gut non-invasively with currently available diagnostic tools.Moreover,non-invasive,rapid diagnostic means to assess intestinal condition are needed to evaluate the effects of treatment of intestinal disorders.This review provides a survey of non-invasive tests and newly identified markers that can be used to assess gut wall integrity.

Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity

AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.