Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study

We read with interest the work by Jaeggi et al 1 and Paganinni et al 2 and commend their efforts. Despite differences in iron concentration, infants’ age and sequencing techniques, both studies demonstrate unfavourable iron effects on gut microbiota with decreased abundance of bifidobacteria and lactobacillus, and increased abundance of pathogenic bacteria in iron-deficient/anaemic Kenyan infants. We have investigated changes in gut microbial composition due to iron fortification or supplementation in healthy, Swedish infants. Iron-sufficient infants at 6 months of age were randomly allocated to receive low-iron-fortified formula (1.2 mg Fe/day; n=24), high-iron-fortified formula (6.6 mg Fe/day; n=24) or no-added-iron formula with liquid ferrous sulfate supplementation (iron drops; 6.6 mg Fe/day; n=24) for 45 days. All participants gave their informed consent before inclusion through parents or legal guardians. Total iron intake was 1.2, 6.4 and 5.7 mg/day (all differences p<0.01) in the low-iron, high-iron and iron-drops group, respectively. Stool samples were collected before and after the intervention. We applied 16S rRNA gene amplicon sequencing of the V3–V4 region to profile the gut microbiome using Illumina MiSeq. We used QIIME3 to assess composition and diversity of gut microbiota and the DESeq2 package4 to investigate differences in relative abundance of gut bacteria among the groups. PICRUSt was used to predict metagenome functional content.5 Vaginally delivered infants (n=53) with paired stool samples were included in the analyses. There were no significant differences in anthropometrics or iron-related biomarkers among the randomisation groups; no adverse …