A34 ANTIBIOTIC TREATMENT AND ORAL IRON SUPPLEMENTATION SHAPE THE COMPOSITION, RECOVERY AND FUNCTION OF THE GUT MICROBIOTA

Abstract

Abstract Background Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. However, the combined effect of antibiotics and luminal iron in the gut on the microbiota and intestinal homeostasis remains unknown. Aims We aim to characterize the dynamics of gut microbiota composition and recovery from antibiotic exposure under iron-sufficient and iron-supplemented diets in mice. We will investigate how microbial shifts induced by antibiotics and iron influence the function of the gut microbiota and metabolites in the gut. Methods Mice were subjected to antibiotic treatment with different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA sequencing before and after antibiotic exposure and during the recovery period. Gut microbiota functions were inferred by using the PICRUSt2 prediction tool, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry. Results Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Four bacterial species characterized as CRC markers and/or CRC initiators were significantly more abundant, and nitrogen and pentose phosphate metabolism were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate, and was independent of luminal iron concentration. For mice recovering from antibiotics under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut. Conclusions Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota and may lead to modifications in the management of anemia in patients with CRC. Funding Agencies CIHR Bourse de Mérite Rougier-Armandie en recherche médicale de la Faculté de médecine