. 2021 Apr 29;11(5):1276. doi: 10.3390/ani11051276

Table 2.

Mechanistic insights from recent livestock studies investigating copper, manganese, and zinc effects on the gut environment.

Mineral	Species	Mineral Supplementation Level and Source	Key Mechanistic Insights	Reference (s)
Zinc	Pig	Pharmacological (2500 mg/kg ZnO) Alternative Zn sources (50–220 mg/kg Zn)	Increased exporter and reduced importer expression. Higher ileal total, free ion, and protein-bound Zn. Changes in GIT microbiota composition and activity. Increased microbiome stress response and reduced carbohydrate processing. Lower intestinal inflammatory state. Increased Th1 response (to 2 weeks post-feeding) and then suppressed. Increased intestinal alkaline phosphatase expression and transepithelial electrical resistance (TEER). Changes in GIT microbiota—reduced E. coli. Increased T-cell numbers, earlier seroconversion and reduced lesions, and severity following Lawsonia intracellularis infection.	[16]
				[22]
				[26]
				[20]
				[27]
	Chicken	Zn deficiency Various forms (30–90 mg/kg Zn)	Reduced diversity and relatedness of caecal bacterial community. Reduced host oxidative stress and enhanced intestinal morphology. Reduced necrotic enteritis lesions, severity, and ileal lactobacilli, and altered jejunal inflammatory marker expression. Increased intestinal morphological features and IEL under heat stressed conditions.	[33]
				[35,37]
				[36]
				[38]
Copper	Pig	0–300 mg/kg (CuSO₄ or HCl)	Reduction in notable fecal butyrate-producing bacteria, lower fecal protein and carbohydrate-related metabolites, and decreased serum TNF-α and higher total antioxidant capacity. Altered GIT microbiota, microbial energy and protein metabolism, increased E. coli and multidrug resistant isolates.	[42]
				[44]
				[45]
	Chicken	1.7–250 mg/kg (nanoparticles, CuSO₄ or Cu acetate)	Modified caecal bacterial community. Decreased duodenal lesion score following mixed Eimeria challenge. Reduced S. Typhimurium colonization of caecal tonsils following oral challenge.	[51]
				[53]
				[55]
Manganese	Chicken	0–400 mg/kg (MnSO₄)	Maintenance of jejunal villus height, higher percentage of CD4+ and CD8+ T-cells in peripheral blood, and modulated cytokine gene expression in spleen, caecal tonsils, and bursa of Fabricius following S. Typhimurium oral challenge. Modified jejunal bacterial community, reduced caecal Salmonella counts, increased duodenal villus height, tight junction gene expression and gut barrier function, activation of immune pathways, and greater splenic proinflammatory gene expression and mitochondrial MnSOD activity following S. Typhimurium oral challenge.	[63]
Manganese	Chicken	0–400 mg/kg (MnSO₄)		[64]