Effects of iron supplements and iron-containing micronutrient powders on the gut microbiome in Bangladeshi infants: a randomized controlled trial

Anemia is highly prevalent globally, especially in young children in low-income countries, where it often overlaps with a high burden of diarrheal disease. Distribution of iron interventions (as supplements or iron-containing multiple micronutrient powders, MNPs) is a key anemia reduction strategy. Small studies in Africa indicate iron may reprofile the gut microbiome towards pathogenic species. We seek to evaluate the safety of iron and MNPs based on their effects on diversity, composition, and function of the gut microbiome in children in rural Bangladesh as part of a large placebo-controlled randomized controlled trial of iron or MNPs given for 3 months (ACTRN12617000660381). In 923 infants, we evaluate the microbiome before, immediately following, and nine months after interventions, using 16S rRNA gene sequencing and shotgun metagenomics in a subset. We identify no increase in diarrhea with either treatment. In our primary analysis, neither iron nor MNPs alter gut microbiome diversity or composition. However, when not adjusting for multiple comparisons, compared to placebo, children receiving iron and MNPs exhibit reductions in commensal species (e.g., Bifidobacterium, Lactobacillus) and increases in potential pathogens, including Clostridium. These increases are most evident in children with baseline iron repletion and are further supported by trend-based statistical analyses.