Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants

Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.


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.

Trial registration number: NCT01111864.

Keywords: Enteric Bacterial Microflora; Enteropathogenic E Coli; Gut Inflammation; Infant Gut; Iron Nutrition.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency / prevention & control
  • Bacteria / isolation & purification
  • Diarrhea, Infantile / chemically induced
  • Diarrhea, Infantile / microbiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enterocolitis / chemically induced*
  • Enterocolitis / microbiology
  • Feces / chemistry
  • Food, Fortified / adverse effects*
  • Humans
  • Infant
  • Intestines / microbiology*
  • Iron, Dietary / administration & dosage
  • Iron, Dietary / adverse effects*
  • Iron, Dietary / pharmacology
  • Leukocyte L1 Antigen Complex / metabolism
  • Microbiota / drug effects*
  • Micronutrients / administration & dosage
  • Micronutrients / adverse effects
  • Micronutrients / pharmacology


  • Iron, Dietary
  • Leukocyte L1 Antigen Complex
  • Micronutrients

Associated data