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

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

Author information

1
Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
2
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
3
International Center for Behavioural Studies, Mombasa, Kenya.
4
NIZO Food Research B.V., Ede, The Netherlands.
5
Department of Food, Technology and Nutrition, University of Nairobi, Nairobi, Kenya.
6
University of KwaZulu-Natal, Durban, South Africa.

Abstract

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

PMID:
25143342
DOI:
10.1136/gutjnl-2014-307720
[Indexed for MEDLINE]

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