Gut microbiota regulates acute myeloid leukaemia via alteration of intestinal barrier function mediated by butyrate

The gut microbiota has been linked to many cancers, yet its role in acute myeloid leukaemia (AML) progression remains unclear. Here, we show decreased diversity in the gut microbiota of AML patients or murine models. Gut microbiota dysbiosis induced by antibiotic treatment accelerates murine AML progression while faecal microbiota transplantation reverses this process. Butyrate produced by the gut microbiota (especially Faecalibacterium) significantly decreases in faeces of AML patients, while gavage with butyrate or Faecalibacterium postpones murine AML progression. Furthermore, we find the intestinal barrier is damaged in mice with AML, which accelerates lipopolysaccharide (LPS) leakage into the blood. The increased LPS exacerbates leukaemia progression in vitro and in vivo. Butyrate can repair intestinal barrier damage and inhibit LPS absorption in AML mice. Collectively, we demonstrate that the gut microbiota promotes AML progression in a metabolite-dependent manner and that targeting the gut microbiota might provide a therapeutic option for AML. The role of gut microbiota in acute myeloid leukaemia (AML) remains unclear. Here, the authors show disordered gut microbiota and reduced butyrate cause intestinal barrier damage in AML mice, with increased plasma LPS that accelerates AML progression.

Automated summary

This study demonstrates that the gut microbiota is associated with AML progression. Dysbiosis of the gut microbiota induced by antibiotic treatment accelerates AML progression in mice, while fecal microbiota transplantation reverses this process. Decreased levels of butyrate, produced by the gut microbiota (especially Faecalibacterium), are found in the feces of AML patients. However, gavage with butyrate or Faecalibacterium postpones AML progression in mice. Additionally, the study reveals that AML mice have damaged intestinal barriers, leading to increased leakage of lipopolysaccharide (LPS) into the blood. The increased LPS exacerbates leukemia progression in vitro and in vivo. Butyrate can repair intestinal barrier damage and inhibit LPS absorption in AML mice.