Retrofitting the Battlements: Tight Junction Remodeling as a Novel Antimicrobial Approach

Improvement of Human-Oral-Epithelial-Barrier Function and of Tight Junctions by Micronutrients

“…This could have far reaching implications for prophylaxis of certain infectious diseases. There are subclasses of pathogens that can, by themselves or via their secreted products, bind to specific TJ components as part of their means of infecting the epithelial cell or the organism at large. ,− Clostridium perfringens enterotoxin has a distinct affinity for claudins-3, -4, and -19 as part of its overall induction of transepithelial gastrointestinal leakiness . On the viral level, hepatitis C has a demonstrated affinity for claudin-1 as part of its mechanism of invading the epithelial cell .…”

“…We would hypothesize that because of their large size, these pathogens or pathogen components can have their binding to the epithelial-cell layer affected not simply by the abundance of their specific claudin-binding “receptor” but also by the overall claudin “neighborhood” around their binding partner. Modification of these “neighborhoods” by micronutrient- and nutraceutical-induced compositional changes of TJ complexes may have effects on the abilities of such pathogens to adhere to and invade across epithelial barriers . This implies that certain micronutrients and nutraceuticals, or combinations thereof, may be prophylactically effective in helping to reduce the frequency or severity of certain infections.…”

“…Modification of these "neighborhoods" by micronutrient-and nutraceutical-induced compositional changes of TJ complexes may have effects on the abilities of such pathogens to adhere to and invade across epithelial barriers. 40 This implies that certain micronutrients and nutraceuticals, or combinations thereof, may be prophylactically effective in helping to reduce the frequency or severity of certain infections. It is less certain but still possible that micronutrient-and nutraceutical-based modifications of TJs may also interfere with the abilities of other pathogens, such as HIV, that do not bind directly to TJ complexes but still induce TJ leakiness following infection of the epithelial cell.…”

Methionine restriction fundamentally supports health by tightening epithelial barriers

“…On the viral side, there is hepatitis C virus, whose viral envelope proteins interact with claudin‐1 (and possibly occludin and claudin‐6 and ‐9) to facilitate viral entry into the cell and the vasculature . It is tempting to speculate that nutrient‐based modification of TJs can play a significant role in reducing pathogen invasion across epithelial junctions and barriers …”