PDF(Pubmed)
Abstract：
The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.
摘要：
骨髓增生异常综合征（MDS）是一组与无效造血相关的造血祖细胞克隆性疾病，并增加了转化为急性骨髓性白血病的风险。MDS分为几类，即谱系发育不良(MDS-SLD)，MDS与环铁皮母细胞（MDS-RS），多谱系发育不良的MDS（MDS-MLD），MDS与过量母细胞(MDS-EB)。国际预后分类系统(IPSS)对患者的排名很低，低,中间,高,基于疾病的演变和存活率非常高。证据表明Toll样受体（TLR）异常信号是这种疾病的潜在机制，提供MDS和免疫功能障碍之间的联系。微生物信号,例如来自革兰氏阴性菌的脂多糖，可以激活或抑制TLR。因此,我们假设MDS患者存在与疾病亚型和预后相关的肠道菌群改变.为了检验这个假设，我们从30例MDS患者和16例健康老年人对照的粪便样本中测序了16SrRNA基因。我们观察到普雷沃氏菌属之间呈负相关。和Akkermansiaspp.MDS患者与对照组比较。高危患者的Prevotella属数量显着增加。与其他风险类别相比。Akkermansia属的丰度显着降低。在高风险患者中，与低风险和中危患者相比。Ruminococcus属明显减少。与对照组相比，MDS-EB患者。我们的研究结果表明，肠道菌群失调与高危MDS之间存在新的关联，以革兰氏阴性菌为主.
