title: Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD.
abstract: 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).
  
  
  
  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.
  
  
  
  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 speciesFaecalibacterium prausnitzii,Ruminococcus bromii,Doreasp. andCollinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates.
  
  
  
  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.
  
  
  
  clinicaltrial.gov (NCT01067547).
authors: Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada.|Department of Gastroenterology, Wollongong Hospital, Wollongong, NSW, Australia.
authors: Thomas
authors: T
authors: Lee
authors: ZIEL Institute for Food and Health, Technische Universität München, Freising, Germany.
authors: Thomas
authors: T
authors: Clavel
authors: Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Kirill
authors: K
authors: Smirnov
authors: Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany.
authors: Annemarie
authors: A
authors: Schmidt
authors: ZIEL Institute for Food and Health, Technische Universität München, Freising, Germany.
authors: Ilias
authors: I
authors: Lagkouvardos
authors: Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Alesia
authors: A
authors: Walker
authors: Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Marianna
authors: M
authors: Lucio
authors: Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Bernhard
authors: B
authors: Michalke
authors: ZIEL Institute for Food and Health, Technische Universität München, Freising, Germany.|Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Philippe
authors: P
authors: Schmitt-Kopplin
authors: Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada.
authors: Richard
authors: R
authors: Fedorak
authors: ZIEL Institute for Food and Health, Technische Universität München, Freising, Germany.|Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany.
authors: Dirk
authors: D
authors: Haller
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000209:etiology; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism / Q000382:microbiology*; D003424:Crohn Disease / Q000150:complications / Q000378:metabolism / Q000382:microbiology*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005290:Ferric Compounds / Q000008:administration & dosage*; D000077605:Ferric Oxide, Saccharated; D005293:Ferritins / Q000097:blood; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005937:Glucaric Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D000090463:Iron Deficiencies; D055442:Metabolome / Q000187:drug effects*; D011788:Quality of Life; D012336:RNA, Ribosomal, 16S / Q000032:analysis
chemical_list: D005290:Ferric Compounds; D006397:Hematinics; D012336:RNA, Ribosomal, 16S; C024823:ferric sulfate; D005293:Ferritins; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
keywords: ANEMIA; IBD CLINICAL; INFLAMMATORY BOWEL DISEASE; INTESTINAL BACTERIA; IRON DEFICIENCY