Published: 25th March, 2015
Authors: RadhaKrishna Rao and Geetha Samak

Introduction:

“In addition to its important role in digestion, absorption and secretion, the gastrointestinal epithelium serves as a barrier to the diffusion of toxins, allergens and pathogens from the luminal contents into the interstitial tissue.

Barrier disruption and diffusion of noxious substances are known to induce mucosal inflammation and tissue injury. In fact, the disruption of gut barrier function plays a crucial role in the pathogenesis of numerous gastrointestinal diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease and infectious enterocolitis.

The specialized junctional complexes called tight junctions provide the intestinal epithelial barrier function. Loss of tight junction integrity and increased intestinal permeability to macromolecules are associated with the pathogenesis of IBD, IBS and celiac disease.

Mucosal protective factors such as growth factors and nutrients preserve the gut barrier integrity and are beneficial in the treatment of various gastrointestinal diseases.

L-Glutamine the most abundant amino acid in blood plays a vital role in the maintenance of mucosal integrity.

Glutamine is traditionally termed as a nonessential amino acid, is now considered a “conditionally essential” amino acid.

Its consumption in small bowel mucosa exceeds the rate of production during catabolic stress such as trauma, sepsis and post surgery.

In the small bowel mucosa, glutamine is an unique nutrient providing fuel for metabolism, regulating cell proliferation, repair and maintaining the gut barrier functions.

The focus of this article is on the role of L-glutamine in the preservation of gut barrier function and the epithelial tight junction integrity and gut barrier function.”

Summary and Perspective:

L-Glutamine is the most abundant and conditionally essential amino acid due to body’s inability to synthesize in adequate amounts during stressful conditions like trauma and sepsis.

It is an oxidative fuel for enterocytes, lymphocytes and plays an important role in maintaining homeostasis with respect to nitrogen balance, acid-base balance and glucose metabolism.

Number of clinical and experimental studies demonstrated its importance as a dietary supplement in maintaining gastrointestinal mucosal barrier function and in preventing bacterial and endotoxin translocation during parenteral nutrition, sepsis, infection, radiation and other various catabolic stress conditions.

Hence Glutamine is an essential nutrient for gut mucosal epithelial cell growth, differentiation, mucosal integrity and barrier function.

Several cell culture studies further confirm its role in the regulation of mucosal epithelial tight junction integrity. L-Glutamine protects tight junctions in Caco-2 cell monolayers and human colonic mucosa from acetaldehyde-induced permeability change and redistribution of tight junction and adherens junction proteins from the intercellular junctions.

This protective effect of L-glutamine appears to be mediated by the transactivation of EGF receptor leading to activation of PKC and MAPK.

There is ample evidence to indicate that L-glutamine is the essential dietary supplement to help maintain mucosal integrity and barrier function under physiologic and pathophysiologic conditions.

Human gut has little capacity to synthesize Glutamine and therefore it relies on the glutamine supply by other tissues and diet.

Over the last decades of clinical trials of glutamine supplementation in critical illness, surgical stress and cancer have shown significant benefit by reducing the rate of mortality, length of hospital stay and infectious morbidity. Parenteral glutamine administration (>0.25–0.3g/kg/day) demonstrated the greatest benefit in hospitalized patients.

Glutamine-based oral rehydration therapy (ORT) was found to be as effective as glucose-based ORT for rehydration, however with additional benefit with regard to repair of intestinal barrier in patients with diarrhea.

Therefore, a growing body of evidence advocates the use of L-glutamine in the clinical practice.

Further understanding and application of glutamine-based therapeutics can be enhanced by future studies geared toward our understanding of the molecular mechanisms associated with glutamine-mediated protection of gastrointestinal epithelial tight junctions and the mucosal barrier function.”