Iron in Health and Disease
Our Research Group
Our research group is interested in understanding how dietary iron excess can be detrimental to human health in particular in intestinal diseases including inflammatory bowel disease and colorectal cancer. By using a variety of models we have shown that iron can amplify a number of oncogenic signalling pathways and that this may in part be through epigenetic events. In addition iron has previously been linked with dysbiosis and that on the whole bacteria associated with enhancement of health are diminished in number.
Thus this evidence has led us to explore the use of iron chelators in particular focussing on naturally occurring iron chelators which could be used as chemopreventive agents in high risk individuals. Thus far we have explored a number of polyphenolic compounds and alginate and have demonstrated strong iron chelating potential. However, for these agents to have maximal bioactivity we are now developing ‘wet’ based formulations which will allow for a larger quantity of bioactive to be delivered specifically to the colon.
Such formulations will also allow us to deliver not only iron chelators but also probiotics to the colon for the enhancement of health. This is particularly pertinent since we are collaborating closely with Professor Iqbal who is the chief investigator of the STOP CLOTIS trial; a trial aimed at remedying inflammatory bowel disease through the use of a faecal transplant. The outputs of this study are ultimately to identify the specific strains of bacteria associated with engraftment and clinical improvement in their disease activity and it will be these strains that we will look to also deliver in our novel wet based formulations.
- Horniblow RD, Mistry P, Quraishi MN, Beggs AD, Van de Wiele T, Iqbal TH, Tselepis C. The Safety and Tolerability of a Potential Alginate-Based Iron Chelator; Results of A Healthy Participant Study. Nutrients. 2019 Mar 21;11(3).pii: E674.doi: 10.3390/nu11030674.
- Horniblow RD, Bedford M, Hollingworth R, Evans S, Sutton E, Lal N, Beggs A, Iqbal TH, Tselepis C. BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis. Cancer Sci. 2017 Jun;108(6):1135-1143.
- Horniblow RD, Henesy D, Iqbal TH, Tselepis C. Modulation of iron transport, metabolism and reactive oxygen status by quercetin-iron complexes in vitro. Mol Nutr Food Res. 2016 Oct 29. doi: 10.1002/mnfr.201600692.
- Horniblow RD, Latunde-Dada GO, Harding SE, Schneider M, Almutairi FM, Sahni M, Bhatti A, Ludwig C, Norton IT, Iqbal TH, Tselepis C. The chelation of colonic luminal iron by a unique sodium alginate for the improvement of gastrointestinal health. Mol Nutr Food Res. 2016 Sep;60(9):2098-108.
- Horniblow RD, Dowle M, Iqbal TH, Latunde-Dada GO, Palmer RE, Pikramenou Z, Tselepis C. Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism. PLoS One. 2015 Sep 17;10(9):e0138240.