Infants and children <2 yrs are the age group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders is a promising approach. However, WHO has recommended against untargeted use of in-home micronutrient powders that contain the iron RDA for a child in a single dose in malarial areas, until their safety is proven. Research priorities from the U.S. NIH Technical Working Group (2009) """"""""Considerations for the safe and effective use of iron interventions in areas of malaria burden"""""""" include: i) effect of iron delivered through different means and formulations on gut microflora;ii) extent to which iron in the gut lumen favors growth of enteric microorganisms with a pathogenic potential. Therefore, we plan to investigate the effect of iron provided in in-home fortification on the infant gut microbiome, using complementary in vitro and in vivo lines of investigation. The focus is on Salmonella spp., as the pathogen most often implicated in studies of bacteremia in severe malaria. The study aims are: i) in vivo, to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants at high risk for diarrheal disease and malaria will modify the composition and metabolic activity of the gut microbiota to favor growth of bacterial enteropathogens, and identify the specific enteropathogens that emerge;ii) in vitro, using immobilized infant fecal microflora in a continuous colonic fermentation model inoculated with the specific pathogens identified in the in vivo studies, as well as a cell culture Salmonella infection model, to determine the mechanisms by which colonic iron selects for bacterial enteropathogens, including iron dose, iron form and the molecular and metabolic response of the gut microbiota to iron. To thoroughly characterize the global impact of iron fortification on the gut microbiota and specifically, on enteropathogens, we will apply TTGE, POR, high-throughput 16S rRNA gene sequence analysis, SCFA production by HPLC as well as metagenomic approaches to measure genotype effects.

Public Health Relevance

This project should provide basic knowledge on the interactions between dietary iron and the infant gut microbiota in order to design safe and effective in-home fortification strategies to control iron deficiency anemia in infants in tropical countries with high burdens of infectious disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HD064921-01
Application #
7880455
Study Section
Special Emphasis Panel (ZHD1-DSR-A (29))
Program Officer
Raiten, Daniel J
Project Start
2009-09-30
Project End
2012-07-30
Budget Start
2009-09-30
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$188,797
Indirect Cost
Name
Swiss Federal Institute of Tech (Eth Zurich)
Department
Type
DUNS #
481907673
City
Zurich
State
Country
Switzerland
Zip Code
8092
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Dostal, Alexandra; Lacroix, Christophe; Bircher, Lea et al. (2015) Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro. MBio 6:e01453-15
Dostal, Alexandra; Gagnon, Mélanie; Chassard, Christophe et al. (2014) Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model. PLoS One 9:e93549
Dostal, Alexandra; Lacroix, Christophe; Pham, Van T et al. (2014) Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats. Br J Nutr 111:2135-45
Dostal, Alexandra; Baumgartner, Jeannine; Riesen, Nathalie et al. (2014) Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in South African children. Br J Nutr 112:547-56
Dostal, Alexandra; Fehlbaum, Sophie; Chassard, Christophe et al. (2013) Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites. FEMS Microbiol Ecol 83:161-75
Jaeggi, Tanja; Moretti, Diego; Kvalsvig, Jane et al. (2013) Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural Kenya. PLoS One 8:e57513
Dostal, Alexandra; Chassard, Christophe; Hilty, Florentine M et al. (2012) Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr 142:271-7