Nicotianamine-chelated iron positively affects iron status, intestinal morphology and microbial populations in vivo (Gallus gallus)

Sci Rep. 2020 Feb 10;10(1):2297. doi: 10.1038/s41598-020-57598-3.


Wheat flour iron (Fe) fortification is mandatory in 75 countries worldwide yet many Fe fortificants, such as Fe-ethylenediaminetetraacetate (EDTA), result in unwanted sensory properties and/or gastrointestinal dysfunction and dysbiosis. Nicotianamine (NA) is a natural chelator of Fe, zinc (Zn) and other metals in higher plants and NA-chelated Fe is highly bioavailable in vitro. In graminaceous plants NA serves as the biosynthetic precursor to 2' -deoxymugineic acid (DMA), a related Fe chelator and enhancer of Fe bioavailability, and increased NA/DMA biosynthesis has proved an effective Fe biofortification strategy in several cereal crops. Here we utilized the chicken (Gallus gallus) model to investigate impacts of NA-chelated Fe on Fe status and gastrointestinal health when delivered to chickens through intraamniotic administration (short-term exposure) or over a period of six weeks as part of a biofortified wheat diet containing increased NA, Fe, Zn and DMA (long-term exposure). Striking similarities in host Fe status, intestinal functionality and gut microbiome were observed between the short-term and long-term treatments, suggesting that the effects were largely if not entirely due to consumption of NA-chelated Fe. These results provide strong support for wheat with increased NA-chelated Fe as an effective biofortification strategy and uncover novel impacts of NA-chelated Fe on gastrointestinal health and functionality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Azetidinecarboxylic Acid / analogs & derivatives*
  • Azetidinecarboxylic Acid / chemistry
  • Azetidinecarboxylic Acid / metabolism
  • Biofortification / methods
  • Biological Availability
  • Chick Embryo
  • Chickens
  • Edetic Acid / chemistry
  • Flour
  • Food, Fortified*
  • Gastrointestinal Microbiome / drug effects
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology
  • Iron / analysis
  • Iron / chemistry
  • Iron / pharmacology*
  • Iron Chelating Agents / chemistry*
  • Models, Animal
  • Triticum / chemistry*
  • Triticum / metabolism


  • Iron Chelating Agents
  • nicotianamine
  • Azetidinecarboxylic Acid
  • 2'-deoxymugineic acid
  • Edetic Acid
  • Iron