Gut microbiota modulates Hyodeoxycholic Acid to Inhibit Leukemia Development.

Abstract

To explore the role of gut microbiota and bile acid metabolism in Acute myeloid leukemia (AML), we analyzed samples from 29 patients via 16S rDNA sequencing and LC-QTOF-MS, and performed functional studies on Enterococcus faecalis and hyodeoxycholic acid (HDCA). Results revealed a dynamic shift in gut microbiota diversity during treatment, which recovered after therapy. Notably, the abundance of Enterococcus at baseline was significantly correlated with clinical response after treatment. Furthermore, fecal microbiota transplantation (FMT) using E. faecalis reduced in vivo leukemia burden and increased levels of bile acids such as HDCA. In vitro analyses demonstrated that HDCA suppresses AML cell growth and promotes apoptosis through inhibition of NF-κB, mitochondrial dysfunction, and cell cycle arrest. These findings were corroborated in a mouse model, where HDCA delayed leukemia progression and improved survival. Clinically, higher baseline serum HDCA correlated with greater gut microbiota α diversity and was associated with complete remission. In summary, Enterococcus levels and baseline HDCA are linked to AML treatment outcomes. E. faecalis FMT ameliorates AML with concurrent rises in fecal HDCA, while HDCA exerts anti-leukemic effects by targeting NF-κB, disrupting mitochondrial integrity, arresting the cell cycle, and triggering apoptosis.