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Cited by 98Inflammatory Bowel DiseaseGut microbiota and healthIron Metabolism and Disorders

Oral iron exacerbates colitis and influences the intestinal microbiome

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Mahalhal, Awad, Williams, Jonathan M., Johnson, Sophie, Ellaby, Nicholas, Duckworth, Carrie A., Burkitt, Michael D., Liu, Xuan, Hold, Georgina L. +3 more·2018·PLoS ONE
DOI 10.1371/journal.pone.0202460PMC PMC6181268

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Abstract

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.

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  • This results in activation of NF-κB and increased production of proinflammatory cytokines TNF, IL-1 and IL-6.

    “This results in activation of one of the central transcription factors of the immune response, NF-κB, and in increased production of proinflammatory cytokines TNF, IL-1 and IL-6 (Buhnik-Rosenblau et al., 2012;Mahalhal et al., 2018;Markota et al., 2019).”

    From Iron in infection and immunity (2020) · cites this paper as Mahalhal et al., 2018

    The Discussion (page unavailable) reports greater colonic inflammation in high-iron-fed mice with DSS-induced colitis, but does not report NF-κB activation or increased TNF, IL-1, or IL-6 production. Searches for NF-κB, TNF, IL-1, IL-6, and cytokine production found only an NF-κB-related title in the References, not a passage establishing the claimed mechanism. (LLM, conf=0.76)

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Authors
Mahalhal, A., Williams, J. M., Johnson, S., Ellaby, N., Duckworth, C. A., Burkitt, M. D., Liu, X., Hold, G. L., Campbell, B. J., Pritchard, D. M., & Probert, C. S.
Affiliations
  • University of Liverpool (GB)
  • Royal Veterinary College (GB)
  • UNSW Sydney (AU)
Corresponding author
  • Mahalhal, Awad
  • Williams, Jonathan M.
  • Johnson, Sophie
  • Ellaby, Nicholas
  • Duckworth, Carrie A.
  • Burkitt, Michael D.
  • Liu, Xuan
  • Hold, Georgina L.
  • Campbell, Barry J.
  • Pritchard, D. Mark
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-10-11
Volume
13
Issue
10
Pages
e0202460
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0202460
PMC
PMC6181268
OpenAlex
W2885877348
Cited by
98
References
47
Citations by year
2026: 1 · 2025: 14 · 2024: 6 · 2023: 21 · 2022: 10 · 2021: 17 · 2020: 19 · 2019: 10
FWCI
7.05
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute for Health and Care Research (CL-2011-07-501)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
dietary iron, iron supplementation, inflammatory bowel disease, colitis, DSS-induced colitis, gut microbiota, gut microbiota diversity, anemia, calprotectin, Firmicutes, Bacteroidetes, Proteobacteria, mouse model
MeSH terms
Gastrointestinal Microbiome, Administration, Oral, Anemia, Animals, Colitis, Disease Models, Animal, Feces, Humans, Iron, RNA, Ribosomal, 16S, Inflammatory Bowel Diseases, Dextran Sulfate, Iron, Dietary, Mice

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