O54 Evaluating oral and intravenous iron therapy on bacterial populations in normal mucosa and colorectal tumour

IntroductionAnaemia is prevalent in around 60% of colorectal cancer (CRC) patients, mostly due to iron deficiency anaemia (IDA) and typically treated with oral iron supplements. However, this may increase the availability of luminal iron to gut bacteria leading to bacterial growth. This may potentially promote microbial dysbiosis, favouring the growth of pathogenic bacteria at the expense of commensal bacteria. Many pathogenic bacteria have heightened iron acquisition mechanism which aid their virulence, which can contribute to tumour promoting inflammation. To assess this, we compared bacterial populations and systemic cytokine production in CRC patients with IDA treated with oral or intravenous iron supplements.MethodsPatients with CRC and IDA received oral-ferrous sulphate (OI) (n=20) or intravenous ferric carboxymaltose (IVI) (n=20). Normal and tumour tissues were obtained post-surgery and analysed for mucosal adherent gut microbiota using 16S rRNA profiling. Bacterial richness was assessed using the Chao1 test and α-diversity was assessed using the Phylogenetic and Shannon index tests. Systemic cytokine levels were measured in the serum before and after treatment using a cytokine multiplex assay.ResultsSpecies richness was significantly higher in normal mucosa from the OI treatment group compared to the IVI group (p=0.033). Likewise, species α-diversity in normal mucosa was significantly greater in OI treated patients (Phylogenetic p=0.037, Shannon p=0.036). However, tumours showed no differences in species richness or α-diversity between treatment groups. Following OI treatment, serum levels of the pro-inflammatory cytokines IL-1b and IL-12p40 were significantly increased (p=0.01 and p=0.03), respectively, and the anti-inflammatory cytokine IL-4 levels were significantly reduced (p=0.01). In contrast, no changes in these cytokines were observed in the IVI group.ConclusionOI therapy increased bacterial richness and α-diversity in normal colonic mucosa and contributed to systemic inflammation in CRC patients. However, the tumour microbiota seems to be protected against increased gut iron, with no difference between OI and IVI therapy. This may be due to pre-existing dysbiosis within the cancer; hence, iron influence may be restricted in the tumours. Ongoing work will assess the abundance and diversity of protective and pathogenic bacteria to determine if these are causative in the systemic inflammation observed with OI therapy.