Iron replacement therapy is a common treatment in patients with anaemia and Crohn’s disease, but oral iron supplements are less tolerated. The pathogenesis of Crohn’s disease is attributed to intestinal bacteria and environmental factors that trigger disease in a genetically predisposed host. The aim of this study was to characterise the interrelationship between luminal iron sulfate, systemic iron, the gut microbiota and the development of chronic ileitis in a murine model of Crohn’s disease.[1]
What is already known about this subject?
- In animal models, a high-iron diet enhances intestinal inflammation, and iron induces ROS production and therefore DNA damage.
- In human trials, it is suggested that oral iron enhances the inflammation index. Patients with IBD often need iron supplementation.
- Endoplasmic reticulum (ER) stress is a possible pathological factor in IBD.
What are the new findings?
- Oral iron deprivation prevents chronic ileitis in TNFΔARE/WT mice and systemic iron repletion maintained the protective effect of luminal iron deprivation.
- Iron triggers ER stress in intestinal epithelial cells and ER stress sensitises the epithelium towards cytotoxic T cell induced apoptosis.
- The comprehensive analysis of the caecal microbiota by pyrosequencing of 16S rRNA tags in WT and TNF∆ARE/WT mice revealed that the depletion of luminal iron sulfate and not inflammation per se induced significant compositional alterations of the caecal microbiota.
How might it impact on clinical practice in the foreseeable future?
- These data imply that systemic iron repletion should be preferred for the treatment of anaemic patients with Crohn’s disease as orally administered iron sulfate led to intestinal inflammation in susceptible TNFΔARE/WT mice.
Comment
Many practitioners will already have experienced the deleterious effects of standard iron supplementation from the GP – Iron sulphate is well known for inducing constipation and bowel distress – yet it is cheap and easily prescribed. Most Nutritional Therapists and observant clinicians have found that an alternative form of iron if often better absorbed and has no adverse effects. There are a number of alternative to sulphate such as citrate or gluconate to consider before systemic supplementation.
So keep in mind that if your IBD patient presents with increasingly unpleasant relapses and is also anaemic – check their iron supplements and change them or refer for systemic supplementation.
Reference
[1] Werner T, Wagner SJ, Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Martínez I, Walter J, Chang JS, Clavel T, Kisling S, Schuemann K, Haller D. Gut. 2010 Nov 12. View Abstract
