Effects of a Micronutrient Powder Containing Low‐dose Iron and Galacto‐oligosaccharides on the Gut Microbiome and Iron Absorption: a Stable Iron Isotope Study and a Randomized Controlled Trial in Kenyan Infants
Authors: Paganini Daniela , Uyoga Mary , Cercamondi Colin , Moretti Diego , Lacroix Christophe , Karanja Simon , Zimmermann Michael B. 
Published: November 2023

Iron deficiency anemia (IDA) is common among infants and iron fortification of complementary foods using micronutrient powders (MNPs) is an effective strategy to control IDA, but the iron dose is high (12.5 mg) and iron absorption is generally less than 10%, resulting in large increases in colonic iron. In controlled studies, iron‐containing MNPs can increase risk for diarrhea in infants because the iron decreases numbers of beneficial ‘barrier’ bifidobacteria and lactobacilli and increases abundances of pathogens (e.g. pathogenic Escherichia coli) and gut inflammation. Thus, there is an urgent need to find safer, low‐dose iron MNP formulations.

We performed a 4‐month randomized double‐blind controlled trial in Kenyan infants to test whether addition of prebiotic, galacto‐oligosaccharides (GOS), to a low iron dose MNP could reduce anemia and mitigate the adverse effects of the iron on the gut microbiome. Infants were randomized to 3 groups:. The first group (MNP) received a MNP containing 30 mg of ascorbic acid and other vitamins and minerals, but no iron. The second group (FeMNP) received the identical MNP but with 2.5 mg iron as NaFeEDTA and 2.5 mg iron as ferrous fumarate. The third group (FeGOSMNP) received the identical MNP as the second group but the maltodextrin was replaced with 7.5 g GOS. There was a significant time*treatment effect on hemoglobin, serum ferritin and transferrin receptor, with all of these varaibles improving in the FeMNP and the FeGOSMNP compared to MNP. We characterized the changes in the gut microbiome with qPCR (10 pathogens) and 16S rRNA sequencing. In FeMNP after 4 months, compared to the MNP group, there was a decrease in the bifidobacteria/enterobacteria ratio, and increases in enterobacteria and the sum of pathogenic Escherichia coli (all p<0.05). In contrast, there were no significant differences in these variables comparing the FeGOSMNP and control groups.

We also performed a stable iron isotope study in Kenyan infants to determine if prior prebiotic consumption would affect iron absorption from a MNP. Infants (n=50; age 6–14 mo) consumed daily for 3 wk porridge fortified with 1) a MNP containing 5 mg iron and 7.5 g GOS or 2) the same MNP without GOS. Then, on two consecutive days, the infants were fed labelled meals with MNPs containing 5 mg iron as FeSO4 (reference) or as ferrous fumarate and NaFeEDTA. GOS consumption increased iron absorption by 62% from the MNP containing ferrous fumarate and NaFeEDTA (p<0.001), possibly reflecting greater colonic iron absorption.

In conclusion: 1) a low‐dose MNP containing 5 mg of iron reduces anemia in Kenyan infants and 2) the addition of a prebiotic to iron‐containing MNPs may protect against the adverse effects of iron on the infant gut microbiome and at the same time sharply increase iron absorption from the MNP.