Amid an increasing number of reports in the literature concerning epithelial barrier enhancement by various nutrient compounds, there has never been a study performing side-by-side comparisons of these agents in a single epithelial model. We compare five nutrient compounds (previously reported in various epithelial models to enhance barrier function) regarding their ability to increase transepithelial electrical resistance (Rt) and decrease transepithelial mannitol permeability (Jm) across LLC-PK1 renal epithelial cell layers. The effects of these nutrients on the abundance of various tight junctional proteins are also compared. In the overall group of nutrients tested - zinc, indole, quercetin, butyrate and nicotine - only nicotine failed to improve barrier function by either parameter. Nicotine also was without effect on tight junctional proteins. Quercetin simultaneously increased Rt and decreased Jm. Zinc, butyrate and indole only exhibited statistically significant enhancement of Rt. Each of these four effective nutrient compounds had unique patterns of effects on the panel of tight junctional proteins studied. No two compounds produced the same pattern of effects. This unique pattern of effects on tight junctional complex composition by each compound establishes the chance for additive or even synergistic improvement of barrier function by combinations of compounds. A synergistic effect of the combination of quercetin and zinc on Rt is shown.

Using various epithelial cell culture models, the nutraceuticals zinc, quercetin, indole, resveratrol and glutamine have been shown to enhance tight junction barrier function. We show that their action is specific to the epithelial model being acted upon. Some increase transepithelial resistance. Some decrease paracellular D‐mannitol leak. Some do both. This depends upon the compound and the specific epithelial cell model. The structural effects of the nutraceuticals are likewise specific to the compound in question and the epithelial model, in terms of which tight junctional proteins are being up‐ or down‐regulated. Certain combinations of nutraceuticals can exhibit additive or even synergistic effects. The medical implications of these barrier‐enhancing nutraceuticals in various disease states are discussed.