Excess Dietary Manganese Impairs Iron Nutrition via Modulating Duodenal Transporters in Weaned Pigs

Despite manganese's essential role as a cofactor for multiple enzymes, its potential to disrupt iron homeostasis when supplemented in excess remains a critical knowledge gap in swine nutrition. This study evaluated the effects of Mn (manganese)-supplemented diets on growth, hematology, mineral accumulation, digestibility, and intestinal iron transporter expression in weaned pigs. A total of 128 crossbred pigs (Duroc × Landrace × Largewhite) with an average body weight of 9.82 ± 0.15 kg were randomly allotted to four dietary treatments comprising a basal diet supplemented with 0, 20, 40, or 80 mg MnSO₄ per kg diet for 28 days. Blood samples were collected from 16 weaned pigs (1 pig per pen, 4 per treatment), after which animals were euthanized for tissue sampling. No differences were observed in growth performance. However, Mn concentrations in serum, liver, heart, kidney, pancreas, and metatarsal bones increased both linearly and quadratically with increasing dietary Mn (<i>p</i> < 0.05), and Fe (iron) concentrations in serum, hemoglobin, liver, and metatarsal bone decreased (<i>p</i> < 0.05). Apparent digestibility data further revealed that Mn absorption peaked at 20 mg/kg, while Fe digestibility declined linearly with increasing Mn levels. Moreover, duodenal <i>DMT1</i> (divalent metal transporter 1) mRNA expression was decreased, whereas <i>FPN1</i> (ferroportin 1) was upregulated. These findings demonstrate that excessive Mn supplementation impairs dietary Fe absorption and homeostasis in weaned pigs, suggesting that the antagonism occurs at both the transcriptional and intestinal absorption levels, providing critical insights for dietary formulation in swine.