PT  - JOURNAL ARTICLE
AU  - Tanja Jaeggi
AU  - Guus A M Kortman
AU  - Diego Moretti
AU  - Christophe Chassard
AU  - Penny Holding
AU  - Alexandra Dostal
AU  - Jos Boekhorst
AU  - Harro M Timmerman
AU  - Dorine W Swinkels
AU  - Harold Tjalsma
AU  - Jane Njenga
AU  - Alice Mwangi
AU  - Jane Kvalsvig
AU  - Christophe Lacroix
AU  - Michael B Zimmermann
TI  - Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants
AID  - 10.1136/gutjnl-2014-307720
DP  - 2015 May 01
TA  - Gut
PG  - 731--742
VI  - 64
IP  - 5
4099  - http://gut.bmj.com/content/64/5/731.short
4100  - http://gut.bmj.com/content/64/5/731.full
SO  - Gut2015 May 01; 64
AB  - 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.