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

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 NAchelated Fe on gastrointestinal health and functionality. Iron (Fe) supplementation and fortification are the two most widely used strategies to combat human Fe deficiencies that affect over 2 billion people worldwide 1-3. Iron supplementation involves large dose delivery of highly absorbable (bioavailable) Fe to humans and is effective in treating severe cases of Fe deficiency anemia 2,4,5. Iron fortification involves low dose delivery of bioavailable Fe fortificants to food products during manufacture (or point-of-use) and is an effective population-based strategy to boost Fe intakes. Iron fortification of wheat flour is now mandatory in 75 countries worldwide (Flour Fortification Initiative; https://fortificationdata.org/), however, the tendency of Fe fortificants such as ferrous sulfate (FeSO 4) to oxidize and cause undesired organoleptic and sensory properties pose significant challenges 6,7. Almost 90% of countries utilize fortificants with poor bioavailability or fortify at sub-optimal concentrations, although recent evidence suggests that Fe fortification can effectively reduce symptoms of Fe-deficiency anemia when correctly implemented 8-10. Iron chelated by ethylenediaminetetraacetate (EDTA) is a commonly recommended fortificant for cereal flour to minimize sensory alterations while providing Fe in a bioavailable form 3,6,8,11,12. Fortificants that utilize micro-and/or nanoencapsulation can further improve bioavailability 12-14 although the cost of using appropriately chelated and/or encapsulated Fe fortificants ($2 USD per ton to fortify wheat flour with EDTA-chelated Fe alone), and the requirement for centralized cereal processing and indust...

Chronic Dietary Zinc Deficiency Alters Gut Microbiota Composition and Function

“…For all in vivo (Gallus gallus) studies that are reviewed here [27][28][29], Cornish cross-fertile broiler eggs were obtained from a commercial hatchery (Moyer's Chicks, Quakertown, PA, USA). The eggs were incubated in optimal conditions at the Cornell University Animal Science poultry farm incubator.…”

“…"Low Zn" (control diet). The specific dietary composition has been previously described [27][28][29]. The NRC recommendations and requirements for poultry were consulted to formulate the diets that were used in these studies with the aim of meeting the nutrient supplies for the broiler, excluding Zn.…”

“…In a third study, we investigated how Nicotianamine-enhanced Fe-and Zn-biofortified wheat may affect microbial populations in vivo (Gallus gallus) [29].…”

Dietary Plant-Origin Bio-Active Compounds, Intestinal Functionality, and Microbiome

“…Furthermore, non-digestible fiber (prebiotics) are dietary substrates that selectively promote proliferation and/or activity of health-promoting bacterial populations in the colon [4]. Prebiotics, such as inulin, raffinose, and stachyose, have a proven ability to promote the abundance of intestinal bacterial populations, which may provide additional health benefits to the host [5][6][7][8][9][10]. Furthermore, various pulse seed soluble (fiber) extracts are responsible for improving gastrointestinal motility, intestinal functionality and morphology, and mineral absorption [9,11].…”

“…Studies have indicated that the consumption of seed-origin soluble extracts can up-regulate the expression of brush border membrane (BBM) proteins that contribute for digestion and absorption of nutrients. The soluble extracts can positively affect intestinal health by increasing the mucus production, goblet cells number/diameter, villus surface area, and crypt depth [9,10]. These functional and morphological effects appear to occur due to the increased motility of the digestive tract, leading to hyperplasia and/or hypertrophy of muscle cells.…”