Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice.
Melissa EllermannRaad Z GharaibehNitsan MaharshakErnesto Peréz-ChanonaChristian JobinIan M CarrollJanelle C ArthurScott E PlevyAnthony A FodorCory R BrouwerR Balfour SartorPublished in: Gut microbes (2019)
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.
Keyphrases
- iron deficiency
- escherichia coli
- microbial community
- oxidative stress
- healthcare
- wild type
- rheumatoid arthritis
- computed tomography
- adipose tissue
- type diabetes
- magnetic resonance imaging
- disease activity
- newly diagnosed
- systemic lupus erythematosus
- prognostic factors
- pseudomonas aeruginosa
- multidrug resistant
- ulcerative colitis
- cystic fibrosis
- body mass index
- skeletal muscle
- risk assessment
- juvenile idiopathic arthritis
- antibiotic resistance genes
- patient reported
- rheumatoid arthritis patients