CoChat
Sign Up
Cited by 291Gut microbiota and healthIron Metabolism and DisordersEscherichia coli research studies

Nutritional iron turned inside out: intestinal stress from a gut microbial perspective

Open access
Kortman, Guus A.M., Raffatellu, Manuela, Swinkels, Dorine W., Tjalsma, Harold·2014·FEMS Microbiology Reviews
DOI 10.1111/1574-6976.12086
Open this paper in CoChat — free accountOpen PDF

Abstract

Iron is abundantly present on earth, essential for most microorganisms and crucial for human health.Human iron deficiency that is nevertheless highly prevalent in developing regions of the world can be effectively treated by oral iron administration.Accumulating evidence indicates that excess of unabsorbed iron that enters the colonic lumen causes unwanted side effects at the intestinal host-microbiota interface.The chemical properties of iron, the luminal environment and host iron withdrawal mechanisms, especially during inflammation, can turn the intestine in a rather stressful milieu.Certain pathogenic enteric bacteria can, however, deal with this stress at the expense of other members of the gut microbiota, while their virulence also seems to be stimulated in an iron-rich intestinal environment.This review covers the multifaceted aspects of nutritional iron stress with respect to growth, composition, metabolism and pathogenicity of the gut microbiota in relation to human health.We aim to present an unpreceded view on the dynamic effects and impact of oral iron administration on intestinal host-microbiota interactions to provide leads for future research and other applications. Summary and scope of this reviewIron is a highly abundant metal on earth and is vital for virtually all organisms, including most bacterial species.Nonetheless, iron deficiency is the most prevalent human nutrition disorder worldwide and is generally treated by oral iron administration.Notably, accumulating evidence suggests that unabsorbed iron can stimulate growth and virulence of bacterial pathogens in the intestinal environment.Simultaneously, host iron status influences the local defence against pathogens.Salmonella enterica serovar Typhimurium, a highly prevalent intestinal pathogen around the world, is one example of a pathogenic bacterial species that can deal with the stress of iron limitation, iron abundance and host defence factors.It is able to adapt to these environmental triggers and exploit the environment to thrive at the expense of other bacterial species.In this review, we will thoroughly discuss many different factors that are involved in iron-mediated host-pathogen interactions in the intestinal tract at the molecular level.We will first give a concise introduction in gut microbiology and nutritional stress.The central part of this review will present current knowledge about the effects of luminal iron on gut immunology and on the gut microbiota with respect to bacterial composition, pathogenicity and metabolism.These and other factors will also be related to pathogen stress in the gut lumen and are summarised in Fig. 1.Furthermore, we will mostly focus on S. Typhimurium and its ways to deal with environmental stress and to turn the external situation in favour of its own growth and colonisation.Finally, we will place the topics we discussed in the context of serious threats that persist in tropical Africa, such as infectious diarrhoea and S. Typhimurium infection that is often associated with invasive disease in this region. General introduction Gut microbiology and healthThe human gut is the natural habitat for a unique large and dynamic bacterial community that greatly

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/1574-6976.12086

Cites

225 of 225 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Proliferation and activity of Escherichia coli is facilitated by the presence of iron in the colonic lumen, suggesting enhanced pathogenicity in the setting of unregulated iron availability.

    “In particular, proliferation and activity of the bacterium Escherichia coli is facilitated by the presence of iron in the colonic lumen, suggesting enhanced pathogenicity in the setting of unregulated iron availability.”

    From Overview of lunar dust toxicity risk (2022) · cites this paper as [52]

    The sections “Effects of nutritional iron on Salmonella infection and other intestinal pathogens” and “Human studies” report increased faecal pathogenic E. coli numbers with iron supplementation, and the former suggests iron has a role in the virulence of certain strains. The paper does not establish that iron in the colonic lumen increases E. coli activity or demonstrate enhanced E. coli pathogenicity under unregulated iron availability; those parts extend beyond its findings. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Although sufficient iron may be present in the gastrointestinal tract, more specifically the colonic lumen, mostly due to excess dietary iron, it may have limited availability to microbiota due to dietary molecules such as polyphenol and phytate as well as metabolic by-products that sequester available iron.

    “Interestingly, although sufficient iron may be present in the gastrointestinal tract, more specifically the colonic lumen, mostly due to excess dietary iron, it may have limited availability to microbiota. This is due to dietary molecules such as polyphenol and phytate as well as metabolic by-products that sequester available iron (reviewed by Kortman et al., 2014).”

    From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Kortman et al., 2014

  • Recent studies suggest that high availability of iron in the gastrointestinal tract may enhance expression of virulent factors in pathogenic bacteria.

    “recent studies suggest that the high availability of iron in the gastrointestinal tract may enhance expression of virulent factors in pathogenic bacteria52.”

    From Overview of lunar dust toxicity risk (2022) · cites this paper as [52]

  • High iron leads to a more diverse oral microbial community.

    “It leads to a more diverse oral microbial community [23]”

    From High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of <i>Candida albicans</i> in oropharyngeal candidiasis (2022) · cites this paper as [23]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 227 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Kortman GAM Maathuis AJH Roeselers G et al. (2014) Dietary iron shifts gut microbial metabolism towards a more toxic profile. Abstract Rowett-INRA Gut Microbiology conference.

Cited by

Sorted by citations

Related

Authors
Kortman, G. A. M., Raffatellu, M., Swinkels, D. W., & Tjalsma, H.
Affiliations
  • Radboud University Medical Center (NL)
  • University of California, Irvine (US)
ORCID
Venue
FEMS Microbiology Reviews
Publisher
Oxford University Press (OUP)
Published
2014-11
Volume
38
Issue
6
Pages
1202-1234
ISSN
  • 0168-6445 (ISSN-L)
  • 1574-6976
DOI
10.1111/1574-6976.12086
OpenAlex
W2110302416
Semantic Scholar
12883cc5aa8bb7572bc2d56537b17a16503466ea
Cited by
291
References
227
Citations by year
2026: 26 · 2025: 24 · 2024: 18 · 2023: 38 · 2022: 34 · 2021: 21 · 2020: 21 · 2019: 28 · 2018: 22 · 2017: 34 · 2016: 12 · 2015: 13
FWCI
1.85
Type
journal article
Language
en
Open access
Locations
  • FEMS Microbiology Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (U54AI065359)
  • Dutch Digestive Diseases Foundation (WO 10-53)
  • Public Health Service Grants (AI083663, AI105374)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
iron deficiency, oral iron supplementation, gut microbiota, host-microbiota interactions, Salmonella typhimurium, iron limitation, iron acquisition, bacterial virulence, intestinal inflammation, intestinal immunity, colonic lumen, bacterial metabolism, bacterial community composition
MeSH terms
Bacteria, Humans, Intestines, Iron, Oxidation-Reduction, Stress, Physiological, Iron, Dietary, Biodiversity, Host-Pathogen Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review