The effect of iron supplementation and tumour location on the mucosal microbiological and immunological environment in colorectal cancer patients with iron deficiency anaemia
Iron deficiency is a common complication of colorectal cancer, being present in ~60% of patients and often leading to the manifestation of anaemia. Preoperative anaemia in colorectal cancer patients is associated with inferior clinical outcomes, hence this leads to the requirement of iron supplementation to treat anaemia. The current standard treatment for iron deficiency anaemia is oral iron supplementation. However, this can contribute to an increased gut luminal iron concentration, which has the potential to alter the gut microbiota and mucosal immune system, potentially leading to inferior oncological outcomes. Previous animal studies have supported this association; however, here is provided the first human clinical studies to assess the microbiological and immunological outcomes of iron supplementation, through a colorectal cancer randomised control trial comparing oral and intravenous iron therapy. The results of these studies suggest that oral iron leads to differential bacterial populations, potentially contributing to a more procarcinogenic microbiota, as well as leading to greater tumour immune cell activity and increased pro-inflammatory cytokine production, compared to intravenous iron therapy. Furthermore, this research provides an insight into the differences between patients with right- and left-sided colorectal cancer; showing the non-tumour microbiota is significantly different between right- and left-sided colorectal cancer patients, whereas the tumour microbiota is more consistent. Furthermore, the results show that right-sided colorectal tumours are more immunogenic, showing an increase in inflammatory cytokines compared to patients with left-sided colorectal tumours. Finally, presented is the long term clinical data from this cohort of patients, assessing differences in tumour location and iron therapy on survival outcomes. Collectively the results of these studies support the use of intravenous iron therapy preoperatively in colorectal cancer patients with iron deficiency anaemia, in order to limit the potential microbial perturbations and inflammatory outcomes associated with oral iron therapy. As well as supporting the stratification of colorectal cancer based upon tumour location, particularly in regard to studies of probiotic and immune therapies.
microbiota, immunology, gut, iron therapy, cytokine, genetics, inflammation, colorectal cancer, intravenous iron, clinical trial
Networked Digital Library of Theses and Dissertations