Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy
DiGuilio et al.
, Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant..
, International Journal of Molecular Sciences, doi:10.3390/ijms23062995 (Review)
Review of epithelial and endothelial barrier compromise and associated disease risk including COVID-19, and the potential benefits of vitamin A, vitamin D, and zinc for improving barrier function.
DiGuilio et al., 10 Mar 2022, peer-reviewed, 8 authors.
Abstract: International Journal of
Micronutrient Improvement of Epithelial Barrier Function in
Various Disease States: A Case for Adjuvant Therapy
Katherine M. DiGuilio 1 , Elizabeth Rybakovsky 1 , Reza Abdavies 2 , Romy Chamoun 3 , Colleen A. Flounders 4 ,
Ariel Shepley-McTaggart 5 , Ronald N. Harty 5 and James M. Mullin 1,6, *
Citation: DiGuilio, K.M.;
Rybakovsky, E.; Abdavies, R.;
Chamoun, R.; Flounders, C.A.;
Shepley-McTaggart, A.; Harty, R.N.;
Mullin, J.M. Micronutrient
Improvement of Epithelial Barrier
Function in Various Disease States:
A Case for Adjuvant Therapy. Int. J.
Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA;
email@example.com (K.M.D.); firstname.lastname@example.org (E.R.)
Department of Biology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA;
Department of Medicine, Lankenau Medical Center, 100 Lancaster Avenue, Wynnewood, PA 19096, USA;
Department of Food and Nutrition Services, Pennsylvania Hospital, 800 Spruce Street,
Philadelphia, PA 19107, USA; email@example.com
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St.,
Philadelphia, PA 19104, USA; firstname.lastname@example.org (A.S.-M.); email@example.com (R.N.H.)
Division of Gastroenterology, Department of Medicine, Lankenau Medical Center, 100 Lancaster Avenue,
Wynnewood, PA 19096, USA
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.
Mol. Sci. 2022, 23, 2995. https://
Academic Editor: Edwin Lephart
Keywords: micronutrient; tight junction; claudin; zinc; Vitamin A; Vitamin D; barrier function;
inflammation; sepsis; virus; COVID; critical care
Received: 11 February 2022
Accepted: 1 March 2022
Published: 10 March 2022
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