Abstract
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.
Highlights
Iron (Fe) supplementation and fortification are the two most widely used strategies to combat human Fe deficiencies that affect over 2 billion people worldwide[1,2,3]
Duodenal cytochrome B (DcytB), divalent metal transporter 1 (DMT1) and Zn transporter (ZIP4) expression was significantly upregulated in intestinal tissue of chickens that received ‘Fe’ relative to all treatment groups, except for DcytB and DMT1 expression in control white flour extract (‘C WF’) and biofortified white flour extract (‘B WF’) treatment groups (Fig. 1E)
Both alkaline phosphatase (AKP) and Zn transporter 1 (ZnT1) expression were significantly upregulated in chickens that received intraamniotic administration of H2O (‘H2O’) relative to ‘Fe’, ‘C WF’ and ‘B WF’ treatment groups (Fig. 1E)
Summary
Iron (Fe) supplementation and fortification are the two most widely used strategies to combat human Fe deficiencies that affect over 2 billion people worldwide[1,2,3]. Iron biofortified rice with increased NA biosynthesis has reversed anemia symptoms in mice, suggesting that NA-chelated Fe is bioavailable in vivo[33,34] Taken together these results reveal NA-chelated Fe as a natural and highly bioavailable Fe fortificant that improves host Fe status. We utilized the chicken model to investigate the impact of NA-chelated and EDTA-chelated Fe on Fe status and gastrointestinal health when delivered alongside extracts of control and biofortified white wheat flour containing increased NA, Fe, Zn and DMA through intraamniotic administration four days prior to hatch (short-term exposure). Together this study highlights the versatility of the chicken model and demonstrates novel positive effects of NA-chelated Fe on host Fe status and gastrointestinal health when administered as an Fe fortificant or as part of a biofortified diet
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