背景:肠道菌群与骨髓增生异常综合征(MDS)之间因果关系的确定尚未实现。此外,免疫细胞参与介导肠道菌群与MDS之间的联系目前尚不清楚。
方法:为了阐明肠道菌群与MDS之间的双向相关性,以及研究免疫细胞的介导作用,双向双样本,进行了两步孟德尔随机化(MR)研究.从全基因组关联研究(GWAS)获得汇总统计数据,包括MDS(456,348人),肠道微生物群(18,340人),和731个免疫细胞签名(3757个个体)。
结果:遗传预测的8个肠道微生物群特征与MDS风险显著相关,但反之亦然。通过宿主微生物组共享基因的生物学注释,我们发现免疫调节可能介导肠道菌群对MDS的影响。随后,23种免疫表型与MDS风险显著相关,其中5种免疫表型受肠道微生物群的因果影响.重要的是,肠道菌群对MDS的因果效应由五种免疫表型显著介导,包括CD4+T细胞%白细胞,CD45RA上的CD127-CD4非调节性T细胞,CD33+HLADR+WHR上的CD45,嗜碱性粒细胞上的CD33,单核细胞AC。
结论:肠道菌群与MDS风险有因果关系,五种特异性免疫表型是肠道微生物群对MDS影响的潜在因果介质。了解肠道微生物群之间的因果关系,免疫细胞和MDS在确定诊断和治疗的潜在靶标方面至关重要。
BACKGROUND: The definitive establishment of a causal relationship between gut microbiota and myelodysplastic syndrome (MDS) has not been achieved. Furthermore, the involvement of immune cells in mediating the connection between gut microbiota and MDS is presently unclear.
METHODS: To elucidate the bidirectional correlation between gut microbiota and MDS, as well as to investigate the mediating role of immune cells, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted. Summary statistics were obtained from genome-wide association studies (GWAS), including MDS (456,348 individuals), gut microbiota (18,340 individuals), and 731 immune cells signatures (3757 individuals).
RESULTS: Genetically predicted eight gut microbiota traits were significantly associated with MDS risk, but not vice versa. Through biological annotation of host-microbiome shared genes, we found that immune regulation may mediate the impact of gut microbiota on MDS. Subsequently, twenty-three immunophenotypes that exhibited significant associations with MDS risk and five of these immunophenotypes were under the causal influence of gut microbiota. Importantly, the causal effects of gut microbiota on MDS were significantly mediated by five immunophenotypes, including CD4 +T cell %leukocyte, CD127 on CD45RA - CD4 not regulatory T cell, CD45 on CD33 + HLA DR + WHR, CD33 on basophil, and Monocyte AC.
CONCLUSIONS: Gut microbiota was causally associated with MDS risk, and five specific immunophenotypes served as potential causal mediators of the effect of gut microbiota on MDS. Understanding the causality among gut microbiota, immune cells and MDS is critical in identifying potential targets for diagnosis and treatment.