Iron is a highly abundant metal on earth and is vital for virtually all organisms. Despite its abundance, iron deficiency is the most prevalent nutrition disorder worldwide. It mostly affects infants, young children and women in developing countries. Iron deficiency has major health consequences such as infection, poor pregnancy outcome, and impaired physical and cognitive development. Several trials have shown that iron deficiency can be effectively controlled by both iron supplementation and fortification programmes. However, safety of iron supplementation has been questioned and there is evidence suggesting that untargeted oral iron supplementation in regions with high prevalence of malaria transmission and infectious diseases can cause an increase in infections, hospital admission and mortality in young children. This might be at least partly ascribed to iron also being an essential requirement for the growth of most bacterial species. Importantly, iron availability is frequently involved in the expression of virulence-associated properties in pathogenic bacteria:
Iron Availability Increases the Pathogenic Potential of Salmonella Typhimurium and Other Enteric Pathogens at the Intestinal Epithelial Interface. (2012) PLoS ONE 7(1): e29968. doi:10.1371/journal.pone.0029968
Recent trials have questioned the safety of untargeted oral iron supplementation in developing regions. Excess of luminal iron could select for enteric pathogens at the expense of beneficial commensals in the human gut microflora, thereby increasing the incidence of infectious diseases. The objective of the current study was to determine the effect of high iron availability on virulence traits of prevalent enteric pathogens at the host-microbe interface. A panel of enteric bacteria was cultured under iron-limiting conditions and in the presence of increasing concentrations of ferric citrate to assess the effect on bacterial growth, epithelial adhesion, invasion, translocation and epithelial damage in vitro. Translocation and epithelial integrity experiments were performed using a transwell system in which Caco-2 cells were allowed to differentiate to a tight epithelial monolayer mimicking the intestinal epithelial barrier. Growth of Salmonella typhimurium and other enteric pathogens was increased in response to iron. Adhesion of S. typhimurium to epithelial cells markedly increased when these bacteria were pre-incubated with increasing iron concentration), whereas this was not the case for the non-pathogenic Lactobacillus plantarum. Cellular invasion and epithelial translocation of S. typhimurium followed the trend of increased adhesion. Epithelial damage was increased upon incubation with S. typhimurium or Citrobacter freundii that were pre-incubated under iron-rich conditions. In conclusion, our data fit with the consensus that oral iron supplementation is not without risk as iron could, in addition to inducing pathogenic overgrowth, also increase the virulence of prevalent enteric pathogens.