Iron Fortification Adversely Affects the Gut Microbiome, Increases Pathogen Abundance and Induces Intestinal Inflammation in Kenyan Infants

Background In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation.Methods We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n= 115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined.Results At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, + FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p= 0.048), the enterobacteria/bifidobacteria ratio (p= 0.020), and Clostridium (p= 0.030). Most of these effects were confirmed using qPCR; for example, + FeMNPs increased pathogenic E. coli strains (p= 0.029). + FeMNPs also increased faecal calprotectin (p= 0.002). During the trial, 27.3% of infants in + 12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p= 0.092). There were no study-related serious adverse events in either group.Conclusions In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation.