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Evidence that Zinc Deficiency Impairs Gut Epithelial Barrier and intestinal Immunity
Author(s) -
Sarkar Paramita,
Saha Tultul,
Aoun Joydeep,
Chakraborty Subhra Hoque,
Chakrabarti Manoj K.,
Dutta Shanta K.,
Hoque Kazi Mirajul
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.747.16
Subject(s) - tight junction , paracellular transport , diarrheal diseases , zinc deficiency (plant disorder) , zinc , pathogenesis , enterocyte , ussing chamber , intestinal permeability , caco 2 , intestinal epithelium , chemistry , diarrhea , biology , microbiology and biotechnology , secretion , immunology , in vitro , medicine , biochemistry , permeability (electromagnetism) , epithelium , small intestine , genetics , organic chemistry , membrane
There is growing interest in dietary factors, in particular micronutrients, from the perspective of disease pathogenesis and potential for treatment. Diarrheal disease in infant results in abnormally low concentrations of serum zinc. Zinc has been tested for its ability to treat and prevent diarrheal diseases in many large field trials over a period of over 4 decades and has generally been found effective. The mechanism by which zinc deficiency causes diarrhea is not known. The present study investigated the impact of zinc deficiency on the host, particularly of intestinal tight junction (TJ) integrity and proteins that are involved in intestinal absorption and secretion along with the pathogenesis of enteric infection. We have used human colonic T84 cells to study barrier function and Shigella to test susceptibility of intestinal infection due to zinc deficiency. T84 grown onto transwell inserts in zinc deficient media showed a low transepithelial electrical resistance (TEER) compare to zinc sufficient media (1014 ± 165 Ω.cm 2 vs 3663 ± 293 Ω.cm 2 ) in confluent T84 monolayers. We furthermore analysed the correlation between TEER and paracellular ionic conductance. We found that zinc deficiency altered paracellular ionic conductance. Bacterial transmigration studies showed a significant increase in apico‐basolateral transmigration of Shigella (6.58 ± 0.13 vs 7.98 ± 0.23 log 10 CFU/ml) which peaked at 6hrs post infection. Transmission electron microscopy data showed widened TJ complex due to few membrane fusion proteins and distorted TJ morphology, whereas the desmosomes were still intact. Electrophysiological studies with Ussing chamber and qPCR quantification demonstrated reduced cAMP dependent electrogenic Cl − secretion (34.5 ± 1.25 μA/cm 2 vs 17.75 ± 2.3 μA/cm 2 ) along with reduced expression of CFTR in zinc deficient cells, resulting dehydrated lumen thus aiding in bacterial colonization. Our results suggest that zinc deficiency caused (1) perturbed barrier function and integrity (2) altered Cl − secretion leading to susceptibility of infection. We conclude that adequate zinc is required to maintain intestinal barrier health to avoid risk against intestinal infection. Support or Funding Information Govt of India National Funding Agency This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .