Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

Abstract

The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care—but also medical prophylactic and therapeutic care in general—to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.

Calcitriol modifies tight junctions, improves barrier function, and reduces TNF‐α‐induced barrier leak in the human lung‐derived epithelial cell culture model, 16HBE 14o‐

“…In fact, the concentration dependence of Figure 2 for calcitriol could not have exemplified the nicely graduating effects of increasing concentration if we had started with a high baseline level of Vitamin D in the culture medium. The fact that barrier‐improving activity of key micronutrients occurs at levels above those normally present in serum (and in Recommended Daily Allowances) is a topic discussed in a recent review from our group (DiGuilio et al, 2022 ).…”

“…Vitamin D therapy may reduce morbidity and thereby be pivotal in allowing a patient's own immune defenses and physiology to achieve more favorable clinical outcomes. This general issue of prophylactic and therapeutic utility of Vitamin D as well as a wider range of micronutrients in a spectrum of diseases is the subject of a very recent review on this topic (DiGuilio et al, 2022 ).…”

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review

“…Microbial pathogens—both viruses and bacteria—are well-evolved to induce leak as part of their etiology [ 24 ]. Examples of viruses would include rotaviruses, flaviviruses, influenza viruses and coronaviruses, to name just a few.…”

“…A literature search using the PubMed search engine for the terms micronutrient/vitamin/flavonoid/zinc AND tight junction (the basis for this review and our previous, more exhaustive review [ 24 ]) now pulls in over 1000 peer-reviewed publications. Many excellent reviews have been written on the subject and it currently seems a well-established fact that micronutrients can improve basal epithelial barrier function [ 24 , 40 , 41 , 42 ]. In addition, micronutrients have demonstrated efficacy in reducing the barrier compromise caused by disease agents and modifiers [ 43 , 44 , 45 ].…”

Estrogen Action and Gut Microbiome Metabolism in Dermal Health

“…7 [ 7 , 8 , 30 , 64 – 66 , 75 , 89 ]. This link between nutrition and venerated skin health includes vitamin D’s mechanism of action and its effects on the skin [ 90 – 92 ].…”