Cancer medicine · 2026
Gut Microbiota Alterations in Myelodysplastic Neoplasms Are Associated With Immune Dysfunction and the Therapeutic Mechanism of Hypomethylating Agents.
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Shi Zhongxun, Huang Fei, Luo Chengrong, Yang Lu, Chen Yu, Qiao Chun, Wang Rong, Wang Yan, Yan Yining, Wang Linlin, Fan Lei, Shen Wenyi
Аннотация
BACKGROUND: Myelodysplastic neoplasms (MDS) represent a group of heterogeneous clonal disorders characterized by immune dysregulation in their pathogenesis. Gut microbiota dysbiosis plays a critical role in immune modulation.
METHODS: We collected the fecal samples of 23 newly diagnosed MDS, 10 hypomethylating agents (HMA) treated MDS and 13 age and sex matched healthy controls (HC), and analyzed the gut microbiota compositions and functional pathways using metagenomic next-generation sequencing (mNGS).
RESULTS: Distinct microbial compositions were observed between newly diagnosed MDS and HC. Notably, the Veillonellaceae family was significantly enriched in MDS patients. Specific bacteroid species demonstrated significant correlations with lymphocyte subtypes, functional activation status, and serum inflammatory cytokines. Functional profiling revealed altered metabolic pathways in newly diagnosed patients, particularly in amino acid metabolism and ATP synthesis. Notably, glutamine/glutamate and tryptophan metabolism pathways were hyperactive in untreated MDS but downregulated following HMA treatment.
CONCLUSIONS: The gut microbiota altered in MDS patients and was associated with immune dysregulation and inflammation, which may contribute to MDS pathogenesis and mediate therapeutic effects of HMA treatment, highlighting the gut microbiota-metabolism axis as a potential therapeutic target for MDS management.
METHODS: We collected the fecal samples of 23 newly diagnosed MDS, 10 hypomethylating agents (HMA) treated MDS and 13 age and sex matched healthy controls (HC), and analyzed the gut microbiota compositions and functional pathways using metagenomic next-generation sequencing (mNGS).
RESULTS: Distinct microbial compositions were observed between newly diagnosed MDS and HC. Notably, the Veillonellaceae family was significantly enriched in MDS patients. Specific bacteroid species demonstrated significant correlations with lymphocyte subtypes, functional activation status, and serum inflammatory cytokines. Functional profiling revealed altered metabolic pathways in newly diagnosed patients, particularly in amino acid metabolism and ATP synthesis. Notably, glutamine/glutamate and tryptophan metabolism pathways were hyperactive in untreated MDS but downregulated following HMA treatment.
CONCLUSIONS: The gut microbiota altered in MDS patients and was associated with immune dysregulation and inflammation, which may contribute to MDS pathogenesis and mediate therapeutic effects of HMA treatment, highlighting the gut microbiota-metabolism axis as a potential therapeutic target for MDS management.