Article Text

Original article
Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD
  1. Thomas Lee1,2,
  2. Thomas Clavel3,
  3. Kirill Smirnov4,
  4. Annemarie Schmidt5,
  5. Ilias Lagkouvardos3,
  6. Alesia Walker4,
  7. Marianna Lucio4,
  8. Bernhard Michalke4,
  9. Philippe Schmitt-Kopplin3,4,
  10. Richard Fedorak1,
  11. Dirk Haller3,5
  1. 1Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada
  2. 2Department of Gastroenterology, Wollongong Hospital, Wollongong, NSW, Australia
  3. 3ZIEL Institute for Food and Health, Technische Universität München, Freising, Germany
  4. 4Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany
  5. 5Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany
  1. Correspondence to Professor Dirk Haller, Chair of Nutrition and Immunology, Technische Universität München, Gregor-Mendel-Str. 2, Freising 85354, Germany; dirk.haller{at}


Objective Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT).

Design The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention.

Results Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates.

Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy.

Trial registration number (NCT01067547).


This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.