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Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and β-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients’ outcome.
Thomas Hueso,Kenneth Ekpe,Camille Mayeur,Anna Gatse,Marie Joncquel-Chevallier Curt,Guillaume Gricourt,Christophe Rodriguez,Charles Burdet,Guillaume Ulmann,Christel Neut,Salah-Eddine Amini,Patricia Lepage,Bruno Raynard,Christophe Willekens,Jean-Baptiste,Micol,Stéphane De Botton,Ibrahim Yakoub-Agha,Frédéric Gottrand,Jean-Luc Desseyn,Muriel Thomas,Paul-Louis Woerther,David Seguy