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

Ruiqing Wang, Xinyu Yang, Jinting Liu, Fang Zhong, Chen Zhang, Yuhong Chen, Tao Sun, Chunyan Ji and Daoxin Ma ()
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Ruiqing Wang: Qilu Hospital of Shandong University
Xinyu Yang: Qilu Hospital of Shandong University
Jinting Liu: Qilu Hospital of Shandong University
Fang Zhong: Shandong Provincial Hospital affiliated with Shandong University
Chen Zhang: Qilu Hospital of Shandong University
Yuhong Chen: Qilu Hospital of Shandong University
Tao Sun: Qilu Hospital of Shandong University
Chunyan Ji: Qilu Hospital of Shandong University
Daoxin Ma: Qilu Hospital of Shandong University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30240-8

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