Table 2.

Links between gut microbiota and zinc.

Intervention	Study Population or Materials	Results	References
Four groups of mice over 8 weeks (5 before and 3 during pregnancy): diet 1—a standard laboratory food (41 mg/kg zinc); diet 2—a zinc-deficient diet (19 mg/kg zinc); diet 3—a standard laboratory food (41 mg/kg zinc) with increased levels of phytates, folic acid, calcium, and iron; diet 4—diet 3 plus 41 mg/kg zinc–amino acid conjugate (ZnAA) supplement.	Animal model—female C57BL/6JRj mice (8 weeks old).	Zinc-deficient diet contributes to abnormal gut–brain signalling by altering intestinal physiology and the composition of the gut microbiota and increasing levels of anti-inflammatory cytokines. These effects were partially reversed and alleviated through supplementation with ZnAA.	Sauer and Grabrucker [179]
A standard/control diet 42 µg/g zinc and a zinc deficient diet 2.5 µg/g zinc administered to two groups of chicks.	Animal model—12 chicks Gallus gallus (upon hatching).	Chronic zinc deficiency alters gut microbiota composition and function and leads to increased abundance of Firmicutes, Prooteobacteria, and Enterobacteriaceae.	Reed et al. [185]
Zinc-enriched probiotics (ZnP). The rats (three groups) were fed a basal diet (control), basal diet with probiotics, or basal diet with zinc-enriched probiotic supplementation (ZnP, 100 mg/L) for 40 days under high heat stress.	Animal model—36 male Wistar rats (6 weeks old).	Rats showed improved growth performance under heat stress due to antioxidant capacity, immune function, expression genes, and change in morphological features of villi height and intestinal wall thickness in the middle part of the jejunum.	Malyar et al. [190]
A controlled zinc-deficient diet (20 mg/kg Zn), an adequate zinc diet (70 mg/kg Zn), or a zinc-supplemented diet (320 mg/kg Zn) for 6 weeks. After hatching, the offspring birds were fed diets with different zinc contents for 6 weeks as well.	Animal model—female chicks—broilers (45 weeks old) and their offspring.	Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks.	Li et al. [200]
The effect of zinc carnosine (ZnC) on various models of gut injury and repair in a clinical trial. Clinical trial: randomized crossover study comparing changes in intestinal permeability (lactulose/rhamnose ratio) before and after 5 days of treatment with indomethacin (50 mg three times a day) vs. ZnC (37.5 mg twice a day) or placebo.	Human colonic epithelial cells (HT29), rat intestinal epithelium (RIE) and canine kidney (MDCK). Rat model of gastric injury (indomethacin/restriction) and mouse model of small intestinal injury (indomethacin). Ten healthy volunteers (clinical trial).	ZnC stabilized intestinal cell mucosa and reduced gastrointestinal damage by enhancing intestinal repair processes in rats and mice. The study showed that ZnC has biological activity.	Mahmood et al. [196]
The effect of zinc on tumour necrosis factor alpha (TNF-α) triggered signalling in human intestinal cells.	A human intestinal cell line Caco-2/TC7 of clonal origin derived from high-passage parental Caco-2 cells.	Intracellular zinc is essential for maintaining intestinal epithelial integrity when cells are exposed to the inflammatory cytokine TNF-α. Zinc deficiency can increase intestinal cell death by impairing intestinal permeability and tight junction integrity through activation of TNF-α.	Ranaldi et al. [197]