The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire.
BACKGROUND
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.


OBJECTIVE
The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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 controlled-trials.com as ISRCTN21782274.
Zimmermann
Michael B
MB
Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland. michael.zimmermann@ilw.agrl.ethz.ch
Chassard
Christophe
C
Rohner
Fabian
F
N'goran
Eliézer K
EK
Nindjin
Charlemagne
C
Dostal
Alexandra
A
Utzinger
Jürg
J
Ghattas
Hala
H
Lacroix
Christophe
C
Hurrell
Richard F
RF
D000293:Adolescent; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy; D001419:Bacteria / Q000145:classification / Q000187:drug effects*; D001939:Bread; D002648:Child; D003106:Colon / Q000382:microbiology*; D007560:Cote d'Ivoire / Q000453:epidemiology; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005527:Food, Fortified; D005759:Gastroenteritis / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D007501:Iron / Q000494:pharmacology* / Q000627:therapeutic use; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D054892:Metagenome / Q000187:drug effects*
D039841:Leukocyte L1 Antigen Complex; D007501:Iron