Enhancement of Tight Junctional Barrier Function by Micronutrients: Compound-Specific Effects on Permeability and Claudin Composition

Abstract

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.

Protective Effects of Lignite Extract Supplement on Intestinal Barrier Function in Glyphosate-Mediated Tight Junction Injury

“…Some natural substances that have shown such improvement include quercetin, butyrate, L-glutamine, and the probiotic Bifidobacterium, and the lignite extract compound studied herein [19,[22][23][24][25][26][27][28][29][30][31][32]. Larazotide, a synthetic pharmaceutical and zonulininhibitor, has also shown to improve tight junction formation [33].…”

Green propolis modulates gut microbiota, reduces endotoxemia and expression of TLR4 pathway in mice fed a high-fat diet

“…It is too early to propose a mechanism by which any compounds in propolis could modulate the microbiota profile, but it is known that phenolic compounds do have an influence on the structure and expression of junction proteins (Mercado et al, 2013;Suzuki & Hara, 2011).…”

Microbiota and the control of blood-tissue barriers

“…Mercado and coworkers 73 have demonstrated direct effects of butyrate and other micronutrients in vitro on individual components of TJ, the transepithelial electrical resistance and transepithelial mannitol permeability of LLC-PK cells (renal epithelial cells). In this system, butyrate elevated the levels of claudin-1, 3, 4, and 5, the latter by almost 300%.…”