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Original Article
Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants
  1. Daniela Paganini1,
  2. Mary A Uyoga2,
  3. Guus A M Kortman3,
  4. Colin I Cercamondi1,
  5. Diego Moretti1,
  6. Tanja Barth-Jaeggi4,
  7. Clarissa Schwab1,
  8. Jos Boekhorst3,
  9. Harro M Timmerman3,
  10. Christophe Lacroix1,
  11. Simon Karanja2,
  12. Michael B Zimmermann1
  1. 1Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
  2. 2Department of Medical Epidemiology, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
  3. 3NIZO Food Research BV, Ede, The Netherlands
  4. 4Health Systems Support Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland
  1. Correspondence to Professor Michael B Zimmermann, ETH Zurich, LFVD20, CH#8092, Zurich, Switzerland; michael.zimmermann{at}hest.ethz.ch

Abstract

Objective Iron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae, and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron.

Design In a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5–9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group).

Results Anaemia decreased by ≈50% in the Fe and FeGOS groups (p<0.001). Compared with the control or FeGOS group, in the Fe group there were (1) lower abundances of Bifidobacterium and Lactobacillus and higher abundances of Clostridiales (p<0.01); (2) higher abundances of virulence and toxin genes (VTGs) of pathogens (p<0.01); (3) higher plasma intestinal fatty acid-binding protein (a biomarker of enterocyte damage) (p<0.05); and (4) a higher incidence of treated RTIs (p<0.05). In contrast, there were no significant differences in these variables comparing the control and FeGOS groups, with the exception that the abundance of VTGs of all pathogens was significantly lower in the FeGOS group compared with the control and Fe groups (p<0.01).

Conclusion A MNP containing a low dose of highly bioavailable iron reduces anaemia, and the addition of GOS mitigates most of the adverse effects of iron on the gut microbiome and morbidity in African infants.

Trial registration number NCT02118402.

  • diarrhea
  • gut
  • microbiome
  • prebiotic
  • enteric pathogens
  • micronutrient powder
  • anemia
  • iron deficiency
  • infancy
  • kenya
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Footnotes

  • Contributors DP, CIC, DM, TB-J, CL and MBZ designed the study; DP, MAU and CIC conducted the study; DP, GAMK, JB, HMT and MBZ analysed the data and performed the statistical analyses; DP, MAU, CIC, GAMK, DM, TB-J, CS, JB, HMT, CL, SK and MBZ participated in the data interpretation; DP, GAMK, CS and MBZ wrote the manuscript. All authors edited the manuscript. All authors read and approved the final version of the manuscript.

  • Funding ETH Global and the Sawiris Foundation for Social Development, ETH Zurich, Switzerland; DSM Nutritional Products, Kaiseraugst, Switzerland. Sight and Life (Kaiseraugst, Switzerland) donated the MNPs used in this study. FrieslandCampina (Wageningen, The Netherlands) donated the GOS used in this study.

  • Ethics approval Kenyatta National Hospital/University of Nairobi, Kenya (P521/10/2013) and the Zurich Cantonal Ethical Commission (2014-0232).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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