Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice

J Nutr Biochem. 2017 Mar:41:25-33. doi: 10.1016/j.jnutbio.2016.11.014. Epub 2016 Dec 2.

Abstract

Mammalian siderophores are believed to play a critical role in maintaining iron homeostasis. However, the properties and functions of mammalian siderophores have not been fully clarified. In this study, we have employed Chrome Azurol S (CAS) assay which is a well-established method for bacterial siderophores study, to detect and quantify mammalian siderophores in urine samples. Our study demonstrates that siderophores in urine can be altered by diet, gut microbiota and inflammation. C57BL/6 mice, fed on plant-based chow diets which contain numerous phytochemicals, have more siderophores in the urine compared to those fed on purified diets. Urinary siderophores were up-regulated in iron overload conditions, but not altered by other tested nutrients status. Further, germ-free mice displayed 50% reduced urinary siderophores, in comparison to conventional mice, indicating microbiota biotransformation is critical in generating or stimulating host metabolism to create more siderophores. Altered urinary siderophores levels during inflammation suggest that host health conditions influence systemic siderophores level. This is the first report to measure urinary siderophores as a whole, describing how siderophores levels are modulated under different physiological conditions. We believe that our study opens up a new field in mammalian siderophores research and the technique we used in a novel manner has the potential to be applied to clinical purpose.

Keywords: Antibiotics; Gut bacteria; Hypoferremia; Iron chelation; Iron toxicity; Purified diets.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia, Iron-Deficiency / etiology
  • Anemia, Iron-Deficiency / immunology
  • Anemia, Iron-Deficiency / microbiology
  • Anemia, Iron-Deficiency / urine*
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / microbiology
  • Colitis / urine*
  • Crosses, Genetic
  • Diet / adverse effects*
  • Diet, High-Fat / adverse effects
  • Female
  • Gastrointestinal Microbiome*
  • Germ-Free Life
  • Hemochromatosis Protein / genetics
  • Hemochromatosis Protein / metabolism
  • Iron Overload / etiology
  • Iron Overload / immunology
  • Iron Overload / microbiology
  • Iron Overload / urine*
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Salmonella Infections, Animal / immunology
  • Salmonella Infections, Animal / microbiology
  • Salmonella Infections, Animal / urine
  • Selenium / deficiency
  • Selenium / immunology
  • Selenium / poisoning
  • Siderophores / urine*
  • Vitamin A Deficiency / etiology
  • Vitamin A Deficiency / immunology
  • Vitamin A Deficiency / microbiology
  • Vitamin A Deficiency / urine*

Substances

  • Biomarkers
  • Hemochromatosis Protein
  • Hfe protein, mouse
  • Lipocalin-2
  • Siderophores
  • Lcn2 protein, mouse
  • Selenium