Gut microbiota regulates AML via alternation of intestinal barrier function mediated by butyrate

Abstract

\n The gut microbiota has been linked to many cancers, yet the role of intestinal microbes in acute myeloid leukemia (AML) progression remains unclear. Here, we observed a significant shift in the gut microbiota in AML patients, characterized by reduced Faecalibacterium abundance. According to a murine AML model, we found that intestinal microbial diversity decreased as the disease progressed. On the other side, gut microbiota dysbiosis induced by antibiotic treatment accelerated AML progression with a higher leukemia cell burden and shorter overall survival (OS), while fecal microbiota transplantation altered this process. Metabolome analyses showed that microbiota-derived butyrate concentration obviously decreased in AML patient feces, and butyrate gavage postponed AML progression in a mouse model. Moreover, our study revealed that intestinal barrier function is decreased in AML mice which may be related to the microbiota disorder caused by AML. Lower intestinal barrier function increased the bacterial-associated lipopolysaccharide (LPS) concentration in the peripheral blood of AML patients or mice through enhancing intestinal permeability. Butyrate repaired the intestinal barrier damage and inhibited LPS absorption in AML mice. Collectively, these findings demonstrate that the gut microbiota promotes AML progression in a metabolite dependent manner, and targeting the gut microbiota might provide a novel therapeutic option for AML.