Effects of High and Low Dose Iron-Containing Micronutrient Powders for In-Home Fortification of Complementary Foods on the Gut Microbiome and Gut Inflammation in Kenyan Infants
Tanja Jaeggi *
ETH Zurich, Zurich, Switzerland.
Guus Kortman
Radboud University Medical Center, Nijmegen, The Netherlands.
Diego Moretti
ETH Zurich, Zurich, Switzerland.
Christophe Chassard
ETH Zurich, Zurich, Switzerland.
Penny Holding
International Centre for Behavioral Studies, Mombasa, Kenya.
Alexandra Dostal
ETH Zurich, Zurich, Switzerland.
Jos Boekhorst
NIZO Food Research B. V., Ede, The Netherlands.
Harro Timmerman
NIZO Food Research B. V., Ede, The Netherlands.
Dorine Swinkels
Radboud University Medical Center, Nijmegen, The Netherlands.
Harold Tjalsma
Radboud University Medical Center, Nijmegen, The Netherlands.
Jane Njenga
University of Nairobi, Nairobi, Kenya.
Alice Mwangi
University of Nairobi, Nairobi, Kenya.
Jane Kvalsvig
University of Kwazulu-Natal, Durban, South Africa.
Christophe Lacroix
ETH Zurich, Zurich, Switzerland.
Michael Zimmermann
ETH Zurich, Zurich, Switzerland.
*Author to whom correspondence should be addressed.
Abstract
Objectives: Primary outcome was change in composition of gut microbiome, after 3 weeks and 4 months. Secondary outcomes were changes in faecal calprotectin, treated diarrhoea, anaemia, iron status and systemic inflammation.
Methods: We performed two randomized controlled trials in 6-month-old Kenyan infants consuming home-fortified maize porridge daily for four months. 1) infants received an MNP containing 2.5 mg iron as NaFeEDTA (+2.5 mgFeMNP) or the identical MNP without iron (-2.5 mgFeMNP). 2) a different MNP containing 12.5 mg iron as ferrous fumarate (+12.5 mgFeMNP) or the identical MNP without iron (-12.5 mgFeMNP).
Results: We enrolled 117 infants, and 101 infants completed the studies between March 2010 and September 2012. Baseline prevalence of anaemia and systemic inflammation were 67.3% and 29.7%, respectively. At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae; using qPCR, Salmonella was detected in 22.8% of infants, B. cereus in 38.6%, S. aureus in 71.3%, C. difficile in 53.5%, and C. perfringens in 86.1%. Body iron stores increased in the +12.5 mgFeMNP (p=0.001), but not in the +2.5 mgFeMNP. Using pyrosequencing, +FeMNPs increased enterobacteria, especially Escherichia/Shigella (p=0.048), the enterobacteria/ bifidobacteria ratio (p=0.020), and Clostridium (p=0.03) compared to -FeMNPs; +FeMNPs also increased faecal calprotectin (p=0.002). Most of these effects were confirmed using qPCR, and many were statistically stronger in ±12.5 mgFeMNP study than in ±2.5 mgFeMNP study. During the trial, 27.3% of infants in the +12.5 mgFeMNP group required treatment for diarrhoea vs. 8.3% in the -12.5 mgFeMNP group (p=0.092).
Conclusions: In rural Africa where infectious disease burden is high, provision of iron-containing MNPs to infants increases gut inflammation and modifies the gut microbiome toward a potentially more pathogenic profile.