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Original article
Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya
  1. Daniela Paganini1,
  2. Mary A Uyoga1,2,
  3. Guus A M Kortman3,
  4. Colin I Cercamondi1,
  5. Hans C Winkler1,
  6. Jos Boekhorst3,
  7. Diego Moretti1,
  8. Christophe Lacroix1,
  9. Simon Karanja2,
  10. Michael B Zimmermann1
  1. 1 Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
  2. 2 Department of Medical Epidemiology, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
  3. 3 NIZO Food Research BV, Ede, The Netherlands
  1. Correspondence to Professor Michael B Zimmermann, Department of Health Sciences and Technology, Laboratory of Human Nutrition, LFV D20, ETH Zurich, Zurich, 8092, Switzerland; michael.zimmermann{at}hest.ethz.ch

Abstract

Objective Many African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).

Design In a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8–10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (FeAb+); (C) no antibiotics and iron-MNPs (Fe+Ab); or (D) no antibiotics and no-iron-MNPs (FeAb). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5–D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.

Results In Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in FeAb+. In FeAb+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In FeAb+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with FeAb+ (12.4%) (p=0.04) and compared with Fe+Ab (5.2%) (p=0.00).

Conclusion Our findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.

Trial registration number NCT02118402; Pre-results.

  • iron nutrition
  • infant gut
  • antibiotics
  • enteropathogenic e coli
  • diarrhoea

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Footnotes

  • Contributors DP, MAU, CIC and MBZ designed the study; DP, MAU and CIC conducted the study; DP, GAMK, HCW, JB and MBZ analysed the data and performed the statistical analyses; all authors participated in the data interpretation; DP, GAMK and MBZ wrote the manuscript. All authors edited the manuscript. All authors read and approved the final version of the manuscript.

  • Funding Funding was provided by ETH Global and the Sawiris Foundation for Social Development, ETH Zurich, Switzerland, and DSM Nutritional Products, Kaiseraugst, Switzerland. Sight and Life (Kaiseraugst, Switzerland) donated the micronutrient powders used in this study.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The larger intervention trial was approved by the ethics and research committees of the Kenyatta National Hospital/University of Nairobi, Kenya (P521/10/2013) and the Zurich Cantonal Ethical Commission (2014–0232); this substudy was approved by Kenyatta National Hospital/University of Nairobi, Kenya (P521/10/2013).

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

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