Can zinc deficiency weaken epithelial barriers and immune responses?

Zinc is integral to epithelial junctions and immune-cell development and signaling. The overall claim is supported: deficiency can impair barrier integrity and dysregulate both innate and adaptive immunity, although the strongest barrier evidence is experimental.

Epithelial-barrier evidence

• In Caco-2 intestinal cells and mouse colon, zinc depletion increased permeability and reduced transepithelial electrical resistance, with reduced occludin and claudin-3. Zinc repletion restored resistance and junctional-protein measures in these models.
• Airway epithelial cultures showed that zinc depletion amplified cigarette-smoke–associated injury, decreasing ZO-1 and claudin-1 and increasing conductance and tracer permeability. This supports zinc status as a contributor to barrier vulnerability, particularly under environmental stress.
• Human confirmation is less direct: a small uncontrolled Crohn’s disease study found improved intestinal permeability after supplementation, but did not establish effects specifically in documented deficiency.

Immune effects

• Deficiency impairs innate defenses, including neutrophil, natural-killer-cell, and macrophage functions. Macrophage effects include reduced phagocytosis and antimicrobial activity, greater oxidative stress, and altered TNF-α, IL-1β, and IL-6 signaling.
• Adaptive effects include thymic atrophy, reduced zinc-dependent thymulin activity, diminished T-cell number/proliferation and Th1 function, and impaired T- and B-cell responses. In nursing-home residents with low serum zinc, 30 mg/day for 3 months increased serum zinc, T-cell numbers, and stimulated proliferation.

Mechanistic explanation

• In intestinal epithelium, depletion activates calpain, promoting occludin proteolysis, while reducing EGR1-dependent claudin-3 transcription. Loss of these tight-junction proteins provides a direct mechanism for leakier epithelial barriers.
• Immune effects are not simply “immunosuppression”: altered inflammatory signaling can coexist with weaker pathogen defense, and NF-κB responses depend on cell type and stimulus.

Bottom line

• Zinc deficiency is a credible, biologically well-supported cause of impaired innate and adaptive immune function and can weaken epithelial barriers. For a 71-year-old, zinc status and supplementation should be clinician-guided: serum zinc is influenced by inflammation and albumin, and prolonged excess zinc can cause copper deficiency.