Journal Article

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

Njenga, Jane, Timmerman, Harro M, Swinkels, Dorine W, Boekhorst, Jos, Holding, Penny, Kvalsvig, Jane, Zimmermann, Michael B, Chassard, Christophe, Tjalsma, Harold, Mwangi, Alice, Kortman, Guus A M, Dostal, Alexandra, Jaeggi, Tanja, Moretti, Diego, Lacroix, Christophe

2015

Overview

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.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Anemia, Iron-Deficiency - prevention & control / Babies / Bacteria / Bacteria - isolation & purification / Breastfeeding & lactation / Clostridium / Clostridium difficile / Clostridium perfringens / Developing countries / Diarrhea / Diarrhea, Infantile - chemically induced / Diarrhea, Infantile - microbiology / Dose-Response Relationship, Drug / Double-Blind Method / E coli / Enterocolitis - chemically induced / Enterocolitis - microbiology / Escherichia coli / Feces - chemistry / Food, Fortified - adverse effects / Hemoglobin / Humans / Infant / Infections / Inflammation / Intestines - microbiology / Iron / Iron, Dietary - administration & dosage / Iron, Dietary - adverse effects / Iron, Dietary - pharmacology / LDCs / Leukocyte L1 Antigen Complex - metabolism / Life Sciences / Malaria / Microbiota - drug effects / Micronutrients - administration & dosage / Micronutrients - adverse effects / Micronutrients - pharmacology / Mortality / Pathogens / Salmonella / Shigella / Studies / Weaning / Zea mays