{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:26:57Z","timestamp":1791473217205,"version":"4.3.4"},"reference-count":83,"publisher":"American Society of Hematology","issue":"16","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,18]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as \u201c7\u00a0+ 3\u201d combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs \u201c7\u00a0+ 3\u201d combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and \u201c7\u00a0+ 3\u201d combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in\u00a0vitro and in\u00a0vivo and fecal microbiota transplantation. We found that CPX-351, at variance with \u201c7\u00a0+ 3\u201d combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor\u2013interleukin-22 (IL-22)\u2013IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023021380","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T16:42:28Z","timestamp":1705423348000},"page":"1628-1645","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis"],"prefix":"10.1182","volume":"143","author":[{"given":"Giorgia","family":"Renga","sequence":"first","affiliation":[{"name":"1Department of Medicine and Surgery, University of Perugia, Perugia, 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