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Title: Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

Journal Article · · Frontiers in Microbiology
 [1];  [2];  [3];  [1];  [4];  [5];  [6];  [7];  [7];  [7];  [1];  [1];  [3];  [1]
  1. Radboud Univ., Nijmegen (Netherlands)
  2. Radboud Univ., Nijmegen (Netherlands); Univ. of Utrecht (Netherlands); Federal Univ. of Rio de Janeiro (Brazil)
  3. TNO Innovation for Life, Zeist (Netherlands)
  4. NIZO food research, Kernhemseweg Ede (Netherlands)
  5. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Lemont, IL (United States)
  6. Illumina Inc., Little Chesterford (United Kingdom); DNA digest, Future Business Centre, Cambridge (United Kingdom)
  7. Illumina Inc., Little Chesterford (United Kingdom)
+ Show Author Affiliations

Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessed by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE
OSTI ID:
1258646
Journal Information:
Frontiers in Microbiology, Vol. 6; ISSN 1664-302X
Publisher:
Frontiers Research FoundationCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 55 works
Citation information provided by
Web of Science

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Cited By (11)

Constipation in chronic kidney disease: it is time to reconsider journal December 2019
Association between the gut microbiota and mineral metabolism: Gut microbiota and mineral metabolism journal October 2017
Dietary strategies for improving iron status: balancing safety and efficacy journal December 2016
Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components journal May 2019
Divergent short-chain fatty acid production and succession of colonic microbiota arise in fermentation of variously-sized wheat bran fractions journal November 2018
The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease journal October 2018
Dietary strategies for improving iron status: balancing safety and efficacy text January 2017
Dietary strategies for improving iron status: balancing safety and efficacy. text January 2017
A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study journal May 2019
Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease journal May 2018
Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron? journal January 2019

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Related Subjects

60 APPLIED LIFE SCIENCES
in vitro fermentation
iron supplementation
gutmicrobiome
metabolome
metagenome
toxicity
SCFA
BCFA