The effects of iron fortification on the gut microbiota in African children: A randomized controlled trial in Côte d'Ivoire

Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 10/2010; 92(6):1406-15. DOI: 10.3945/ajcn.110.004564
Source: PubMed


Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host.
The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children.
In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens.
At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05).
Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at as ISRCTN21782274.

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Available from: Fabian Rohner, Sep 24, 2015
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    • "Generally, the complex of bacteria in the gut is stable in healthy individuals (Arumugam et al. 2011; Yatsunenko et al. 2012), but, one of the anxieties surrounding engineered nanoparticulate compounds that are added to the diet is their potential to induce changes to the microbiome (Sawosz et al. 2007; Han et al. 2010; Pineda et al. 2012; Wang et al. 2012). Moreover, soluble oral iron has been associated with detrimental changes to the gut microbiota in gastrointestinal disease (Zimmermann et al. 2010; Werner et al. 2011)and with increased growth "
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    ABSTRACT: Alterations in the gut microbiota have been recently linked to oral iron. We conducted two feeding studies including an initial diet-induced iron-depletion period followed by supplementation with nanoparticulate tartrate-modified ferrihydrite (Nano Fe(III): considered bioavailable to host but not bacteria) or soluble ferrous sulfate (FeSO4: considered bioavailable to both host and bacteria). We applied denaturing gradient gel electrophoresis and fluorescence in situ hybridization for study-1 and 454-pyrosequencing of fecal 16S rRNA in study-2. In study-1, the within-community microbial diversity increased with FeSO4 (P = 0.0009) but not with Nano Fe(III) supplementation. This was confirmed in study-2, where we also showed that iron depletion at weaning imprinted significantly lower within- and between-community microbial diversity compared to mice weaned onto the iron-sufficient reference diet (P < 0.0001). Subsequent supplementation with FeSO4 partially restored the within-community diversity (P = 0.006 in relation to the continuously iron-depleted group) but not the between-community diversity, whereas Nano Fe(III) had no effect. We conclude that (1) dietary iron depletion at weaning imprints low diversity in the microbiota that is not, subsequently, easily recovered; (2) in the absence of gastrointestinal disease iron supplementation does not negatively impact the microbiota; and (3) Nano Fe(III) is less available to the gut microbiota.
    MicrobiologyOpen 09/2014; 4(1). DOI:10.1002/mbo3.213 · 2.21 Impact Factor
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    • "weekly or daily) [18-23]. Reasons for gastrointestinal disturbance are well described: even in subjects with IDA only about 20-30% of oral supplemented iron is absorbed, while the remainder transits through the gut lumen inducing (a) free radical mediated damage to the gut mucosa [9,24-26] and (b) undesirable changes to colonic microflora [27-29]. Gastrointestinal symptoms impact on the general wellbeing of individuals [30-37] and are known to affect compliance with oral iron therapy and, therefore, treatment efficacy [7,19,38-40]. "
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    ABSTRACT: Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating.
    BMC Gastroenterology 06/2014; 14(1):103. DOI:10.1186/1471-230X-14-103 · 2.37 Impact Factor
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    • "The dietary shift associated with the transition from human milk to family foods fundamentally alters the composition of the intestinal microbiota (Thompson, 2012) in both breastfed and formula fed infants, and likely driven primarily by the differences in macronutrients and oligosaccharides between human milk and commercial infant formula. Some of the shift may be related to changes in iron availability as originally hypothesized by Balmer and Wharton (1991), and seen in older infants and children with the addition of iron fortified biscuits as an IDA preventive treatment (Zimmermann et al., 2010). However, specific studies looking at differences in the microbiome between infants randomized to formula with different amounts of iron have not been conducted so direct comparisons are impossible at present. "
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    ABSTRACT: Recently, there has been considerable debate regarding the appropriate amount of iron fortification for commercial infant formula. Globally, there is considerable variation in formula iron content, from 4 to 12 mg iron/L. However, how much fortification is necessary is unclear. Human milk is low in iron (0.2-0.5 mg/L), with the majority of infant iron stores accumulated during gestation. Over the first few months of life, these stores are depleted in breastfeeding infants. This decline has been previously largely perceived as pathological; it may be instead an adaptive mechanism to minimize iron availability to pathogens coinciding with complementary feeding. Many of the pathogens involved in infantile illnesses require iron for growth and replication. By reducing infant iron stores at the onset of complementary feeding, infant physiology may limit its availability to these pathogens, decreasing frequency and severity of infection. This adaptive strategy for iron regulation during development is undermined by the excess dietary iron commonly found in infant formula, both the iron that can be incorporated into the body and the excess iron that will be excreted in feces. Some of this excess iron may promote the growth of pathogenic, iron requiring bacteria disrupting synergistic microflora commonly found in breastfed infants. Evolutionarily, mothers who produced milk with less iron and infants who had decreased iron stores at the time of weaning may have been more likely to survive the transition to solid foods by having limited iron available for pathogens. Contemporary fortification practices may undermine these adaptive mechanisms and increase infant illness risk. Am. J. Hum. Biol. 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 01/2014; 26(1). DOI:10.1002/ajhb.22476 · 1.70 Impact Factor
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