SRA

Induction chemotherapy (“3+7”) remains the gold standard in patients with acute myeloid leukemia (AML) but it responsible for gut damage leading to several complications such as septicemia. The aim of this translational study was to investigate the impact of chemotherapy on the intestinal barrier in AML patients undergoing 3+7 regimen translate to a murine model (Wt mice). Next we assessed the potential benefit effect of strengthening mucosal barrier in transgenic mice model (Tg222). In patients, we observed a transient decrease of plasma citrulline and a prolonged decrease of all bacteria in feces except for E. coli and enterococcus spp after hematological recovery. It was accompanied with a decrease of a and ß-diversity. In Wt mice we observed a transient decrease of citrulline level whereas the bacterial load in terminal ileum remained stable with the expansion of E. coli and enterococcus spp. In Tg222, we observed a higher citrulline level, tissue repair and a preserved a-diversity accompanied with a limited bacterial translocation three days after the chemotherapy completion compared to Wt mice. This translational study describes the transient intestinal impairment associated with a prolonged dysbiosis induced by “3+7”. Our transgenic model as a proof of concept suggests that strengthening intestinal barrier could be a new approach to limit septicemia.