Perspective: Prospects for Nutraceutical Support of Intestinal Barrier Function.

Impairment of intestinal barrier function is linked to certain pathologies and to aging, and can be a cause of bacterial infections, systemic and hepatic inflammation, food allergies, and autoimmune disorders. The formation and maintenance of intestinal tight junctions is supported by glucagon-like peptide-2 (GLP-2), which via insulin-like growth factor I activity boosts phosphoinositide 3-kinase/Akt/mammalian target of rapamycin complex 1 (PI3K/Akt/mTORC1) signaling in enterocytes. 5'-AMP-activated protein kinase (AMPK) activity as well as estrogen receptor-β (ERβ) activity are also protective in this regard. Conversely, activation of mitogen-activated protein kinases (MAPKs) and cellular Src (c-Src) under inflammatory conditions can induce dissociation of tight junctions. Hence, nutraceuticals that promote GLP-2 secretion from L cells-effective pre/probiotics, glycine, and glutamine-as well as diets rich in soluble fiber or resistant starch, can support intestinal barrier function. AMPK activators-notably berberine and the butyric acid produced by health-promoting microflora-are also beneficial in this regard, as are soy isoflavones, which function as selective agonists for ERβ. The adverse impact of MAPK and c-Src overactivation on the intestinal barrier can be combatted with various antioxidant measures, including phycocyanobilin, phase 2-inducer nutraceuticals, and N-acetylcysteine. These considerations suggest that rationally designed functional foods or complex supplementation programs could have clinical potential for supporting and restoring healthful intestinal barrier function.