title: Oral iron acutely elevates bacterial growth in human serum.
abstract: Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.
authors.forename: James H
authors.initials: JH
authors.lastname: Cross
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.|School of Medical and Applied Sciences, Central Queensland University, North Rockhampton, Queensland, Australia.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Bradbury
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.|MRC International Nutrition Group, London School of Hygiene &Tropical Medicine, Keppel Street, WC1E 7HT, London, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Fulford
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.
authors.forename: Amadou T
authors.initials: AT
authors.lastname: Jallow
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.
authors.forename: Rita
authors.initials: R
authors.lastname: Wegmüller
authors.affiliation: MRC Keneba, MRC Unit, The Gambia, Atlantic Blvd, Serrekunda, Gambia.|MRC International Nutrition Group, London School of Hygiene &Tropical Medicine, Keppel Street, WC1E 7HT, London, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Department of Epidemiology, Gillings' School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Cerami
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003470:Culture Media / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D005296:Ferrous Compounds / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006801:Humans; D007501:Iron / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development; D044967:Serum / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology; D015008:Yersinia enterocolitica / Q000187:drug effects* / Q000254:growth & development
chemical_list: D003470:Culture Media; D005296:Ferrous Compounds; D014168:Transferrin; C020748:ferrous sulfate; D007501:Iron