Oral Iron Supplementation Increases Severity of Salmonella Typhimurium Infection

Abstract Objectives Salmonella Typhimurium (S. Typhimurium) infection is a leading global cause of morbidity and mortality in humans. The objective of this study was to determine whether unabsorbed iron in the cecum of mice increases the severity of S. Typhimurium infection. Methods Three-week-old female C57BL/6 mice were fed diets containing 300 (iron supplemented, FeS) or <4 ppm iron (iron deficient, FeD) for 6 weeks (n = 30/diet). Following feeding, mice were given an oral gavage of streptomycin 24 h prior to oral gavage of 108 CFU S. Typhimurium (FeSS.Tm or FeDS.Tm, n = 15/diet/treatment). Mice were monitored for up to 1-week post-infection prior to euthanasia and tissue collection. Severity of infection was assessed by cecal weight, spleen index, and change in bodyweight post-infection. Data are presented as means ± SD. Results Hematocrits were greater in FeS (51.3 ± 0.8%) compared to FeD (43.8 ± 2.7%), FeSS.Tm (40.3 ± 3.8%) and FeDS.Tm (40.2 ± 7.3%, P < 0.01 for all comparisons). FeS had higher cecal iron (331.3 ± 59.3 μg Fe/mg tissue) compared to FeD (5.7 ± 2.4 μg Fe/mg tissue), FeSS.Tm (64.6 ± 26.4 μg Fe/mg tissue) and FeDS.Tm (6.7 ± 3.3 μg Fe/mg tissue, P < 0.0001 for all comparisons). Cecal weight was ∼40% lower in FeSS.Tm (0.3 ± 0.1 g) compared to FeD (0.5 ± 0.1 g), FeS (0.5 ± 0.2 g) and FeDS.Tm (0.5 ± 0.1 g, P < 0.05 for all comparisons). Spleen index was greater in FeSS.Tm (15.3 ± 7.2 A.U.) compared to FeS (4.3 ± 0.5 A.U.), FeD (4.0 ± 0.5 A.U.) and FeDS.Tm (8.8 ± 5.2 A.U., P < 0.01 for all comparisons). FeSS.Tm lost more bodyweight (−21.7 ± 5.4%) compared to FeDS.Tm (−14.5 ± 6.3%, P < 0.01) post-infection. Conclusions Findings suggest that unabsorbed iron in the cecum of mice promotes a more severe S. Typhimurium infection. Alternative iron supplementation strategies should be considered in countries where S. Typhimurium infections are common. Funding Sources Intramural funds to S.R.H.