Influence of Iron on the Gut Microbiota in Colorectal Cancer

Abstract

Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.

Differences in the on- and off-tumour microbiota between right- and left-sided colorectal cancer

“…Hence, this leaves the potential for the study of the gut microbiota in pathological conditions to be confounded by discrepancies in therapeutic interventions. 11,12 For instance, patients with right-sided colorectal cancer tend to more commonly develop iron de ciency anaemia, compared to those with left-sided colorectal cancer. Enteral iron is often given to treat anaemia, which has the potential to increase colonic iron concentration and alter the gut microbiota.…”

“…Hence, this suggests the use of parental iron supplementation in anaemic colorectal cancer patients in order to study the gut microbiota. 11,12 This pilot study aims to determine the gut bacterial pro les of the on-and off-tumour microbiota in colorectal cancer and how they differ between patients with right-and left-sided colorectal cancer. In order to address the issue regarding iron supplementation, all patients were treated with parental iron prior to surgery.…”

Flipside of the Coin: Iron Deficiency and Colorectal Cancer

“…On the contrary; it has been found to be ineffective in individuals with cancer and especially CRC, since intestinal iron absorption is greatly reduced in these patients (nearly 95% of the iron being excreted) ( 33 ). Furthermore, the increased availability of iron in the gut due to reduced intestinal iron absorption may support the proliferation of pathogenic gut bacteria conducive to tumor progression in preference to protective passenger bacteria that are more likely to hinder disease progression ( 148 ). As for the very small quantity of iron absorbed, most remains trapped within the enterocytes, where it is largely blocked by inflammatory cytokines and thus cannot be metabolized ( 33 , 149 ).…”

Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients

“…Iron is essential for the growth and development of the vast majority of gut bacteria, with pathogenic bacteria tending to have heightened iron acquisition mechanisms [ 6 ]. Hence, in anemic colorectal cancer patients, the use of oral iron supplementation has the potential to alter bacterial populations of the colorectal tumor-associated (on-tumor) microbiota, as well as the non-tumor-associated mucosal (off-tumor) microbiota, through increasing gut luminal iron concentration [ 7 , 8 ]. This may suggest that a parenteral route of iron administration may be more beneficial to treat anemia, without increasing iron availability to colonic bacteria.…”