Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD

Abstract

ObjectiveIron 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).DesignThe 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.ResultsBoth 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.ConclusionsShifts 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 numberclinicaltrial.gov (NCT01067547).

Safety of Oral and Intravenous Iron

“…The recent PIVOTAL study also showed no increased risk of infection with aggressive intravenous iron supplementation in dialysis patients [4]. In addition, compared to oral iron, intravenous iron did not lead to adverse changes in bowel microbiome in patients with inflammatory bowel disease [14]. Given the ability of iron to promote oxidation, concerns have been expressed about the use of intravenous iron leading to oxidative damage to endothelial cells and atherosclerosis, but this concern has not been validated in clinical studies [30, 38].…”

“…This shift has been associated with increased bowel inflammation. A shift toward a pathogenic microbiome has also been seen in patients with inflammatory bowel disease with use of oral iron [14]. …”

Management of Iron Deficiency Anaemia in Inflammatory Bowel Disease

“…Oral iron alters the microbiota profile and metabolism, which likely influences the underlying intestinal disease [18, 19]. In animal models of colitis, oral iron exacerbates colitis and promotes carcinogenesis [20, 21].…”

Anemia and IBD: Current Status and Future Prospectives

“…In one recent open-labeled clinical trial, the effects of oral (iron sulfate) versus IV iron (Iron sucrose) over a 3-month period, in adult patients with IBD (CD: 31; UC: 22) versus control subjects with IDA without inflammation and its impact in clinical parameters, gut microbioma, and metabolome [38] were compared. The authors concluded that both oral and IV iron were effective in the correction of Hb levels, and moreover they found that oral iron distinctively affected bacterial phylotypes and fecal metabolites, as compared to IV iron.…”