A Metabolome and Microbiome Analysis of Acute Myeloid Leukemia: Insights into the Carnosine-Histidine Metabolic Pathway.

ABSTRACT

Metabolism underlies the pathogenesis of acute myeloid leukemia (AML) and can be influenced by gut microbiota. However, the specific metabolic changes in different tissues and the role of gut microbiota in AML remain unclear. In this study, we analyzed the metabolome differences in blood samples from patients with AML and healthy controls using UPLC-Q-Exactive. Additionally, we examined the serum, liver, and fecal metabolome of AML model mice and control mice using UPLC-Q-Exactive. The gut microbiota of the mice were analyzed using 16S rRNA sequencing. Our UPLC-MS analysis revealed significant differences in metabolites between the AML and control groups in multiple tissue samples. Through cross-species validation in humans and animals, as well as reverse validation of Celastrol, we discovered that the Carnosine-Histidine metabolic pathway may play a potential role in the occurrence and progression of AML. Furthermore, our analysis of gut microbiota showed no significant diversity changes, but we observed a significant negative correlation between the key metabolite Carnosine and Peptococcaceae and Campylobacteraceae. In conclusion, the Carnosine-Histidine metabolic pathway influences the occurrence and progression of AML, while the gut microbiota might play a role in this process.