Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice

Melissa Ellermann, Raad Z. Gharaibeh, Nitsan Maharshak, Ernesto Peréz-Chanona, Christian Jobin, Ian M. Carroll, Janelle C. Arthur, Scott E. Plevy, Anthony A. Fodor, Cory R. Brouwer, R. Balfour Sartor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Iron deficiency, a common comorbidity of gastrointestinal inflammatory disorders such as inflammatory bowel diseases (IBD), is often treated with oral iron supplementation. However, the safety of oral iron supplementation remains controversial because of its association with exacerbated disease activity in a subset of IBD patients. Because iron modulates bacterial growth and function, one possible mechanism by which iron may exacerbate inflammation in susceptible hosts is by modulating the intestinal microbiota. We, therefore, investigated the impact of dietary iron on the intestinal microbiota, utilizing the conventionalization of germ-free mice as a model of a microbial community in compositional flux to recapitulate the instability of the IBD-associated intestinal microbiota. Our findings demonstrate that altering intestinal iron availability during community assembly modulated the microbiota in non-inflamed wild type (WT) and colitis-susceptible interleukin-10-deficient (Il10−/-) mice. Depletion of luminal iron availability promoted luminal compositional changes associated with dysbiotic states irrespective of host genotype, including an expansion of Enterobacteriaceae such as Escherichia coli. Mechanistic in vitro growth competitions confirmed that high-affinity iron acquisition systems in E. coli enhance its abundance over other bacteria in iron-restricted conditions, thereby enabling pathobiont iron scavenging during dietary iron restriction. In contrast, distinct luminal community assembly was observed with dietary iron supplementation in WT versus Il10−/- mice, suggesting that the effects of increased iron on the microbiota differ with host inflammation status. Taken together, shifts in dietary iron intake during community assembly modulate the ecological structure of the intestinal microbiota and is dependent on host genotype and inflammation status.

Original languageEnglish
Pages (from-to)32-50
Number of pages19
JournalGut Microbes
Issue number1
StatePublished - 2 Jan 2020


FundersFunder number
National Gnotobiotic Rodent Resource Center
National Institutes of HealthP40 OD01995, K01 DK103952, P30DK34987, R01 DK053347
Howard Hughes Medical Institute
NIH Office of the DirectorP40OD010995
Crohn's and Colitis Foundation of AmericaPODK094779
Honeywell Hometown Solutions
University of North Carolina


    • Animal models of GI-diseases with microbial components
    • Defining/profiling gut microbiome
    • Dietary iron
    • Escherichia coli
    • IBD
    • Role of gut microbiome in GI disease
    • colitis
    • gut microbiome


    Dive into the research topics of 'Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice'. Together they form a unique fingerprint.

    Cite this