基于孟德尔随机化探索肠道菌群、血浆代谢物和弥漫性大B细胞淋巴瘤的因果关系OA
Exploration of Causal Relationships Between Gut Microbiota,Plasma Metabolites,and Diffuse Large B-cell Lymphoma Based on Mendelian Randomization
通过孟德尔随机化(MR)分析肠道菌群、血浆代谢物与弥漫性大 B 细胞淋巴瘤(DLBCL)的因果关联及代谢物的中介作用.采用双样本孟德尔随机化(MR)方法,整合 DLBCL、473 种肠道菌群及 1 400 种血浆代谢物的全基因组关联研究数据,以逆方差加权法为主要分析方法,辅以 MR-Egger、加权中位数(WM)等进行因果推断,并通过中介 MR分析探索代谢物中介效应.通过水平多效性和异质性检验确保结论的稳定性.21 种肠道菌群与 DLBCL存在显著因果关系,其中毛螺杆菌目致病作用较强(OR=2.907 6,P=0.034 2),CAG-177 种保护作用显著(OR=0.596 8,P=0.000 5);45 种代谢物及比例与DLBCL相关,3′,5′-环磷酸腺苷/牛磺胆酸比值(OR=1.718 9,P=0.005 1)和可的松(OR=1.640 7,P=0.016 7)为主要危险因素.中介分析发现,3′,5′-环磷酸腺苷/牛磺胆酸比值介导毛螺杆菌目与 DLBCL 关系的 23.25%,苯乙酰肉碱介导SAR324 门与DLBCL关系的 10.81%.揭示肠道菌群和血浆代谢物在DLBCL发病中的因果参与,为其防治提供潜在生物标志物及靶点.
The paper aims to investigate the causal relationships between gut microbiota,plasma metabolites,and diffuse large B-cell lymphoma(DLBCL)using Mendelian randomization(MR)analysis,and to explore the me-diating role of metabolites.In the study,A two-sample Mendelian randomization approach was employed,in-tegrating genome-wide association study(GWAS)data on DLBCL,473 gut microbiota taxa,and 1 400 plasma metabolites.The inverse-variance weighted(IVW)method served as the primary analysis,supplemented by MR-Egger,weighted median(WM),and other methods for causal inference.Mediation MR analysis was con-ducted to assess metabolite-mediated effects.Horizontal pleiotropy and heterogeneity tests were performed to en-sure the robustness of the findings.The results as follows:twenty-one gut microbiota taxa had significant causal associations with DLBCL,with the order Lachnospirales exhibiting the strongest pathogenic effect(OR=2.907 6,P=0.034 2),while species CAG-177 demonstrated the most notable protective effect(OR=0.596 8,P=0.000 5).Besides,forty-five metabolites and their ratios were associated with DLBCL,with the 3′,5′-cyclic adenosine monophosphate/taurocholic acid ratio(OR=1.718 9,P=0.005 1)and cortisone(OR=1.640 7,P=0.016 7)identified as major risk factors.Mediation analysis revealed that the 3′,5′-cyclic adenosine mono-phosphate/taurocholic acid ratio mediated 23.25%of the effect of Lachnospirales on DLBCL,while phenylace-tylcarnitine mediated 10.81%of the effect of phylum SAR324 on DLBCL.In conclusion,the study reveals the causal participation of gut microbiota and plasma metabolites in the pathogenesis of DLBCL,and provides poten-tial biomarkers and therapeutic targets for its prevention and treatment.
CHANG Jiahao;WANG Zongqing;SUN Zhengqiang;ZHANG Xinying;XU Qian
Henan Provincial Engineering Laboratory of Insects Bio-reactor,Nanyang Normal University,Nanyang Henan 473061,ChinaHenan Provincial Engineering Laboratory of Insects Bio-reactor,Nanyang Normal University,Nanyang Henan 473061,ChinaHenan Provincial Engineering Laboratory of Insects Bio-reactor,Nanyang Normal University,Nanyang Henan 473061,ChinaHenan Provincial Engineering Laboratory of Insects Bio-reactor,Nanyang Normal University,Nanyang Henan 473061,ChinaHenan Provincial Engineering Laboratory of Insects Bio-reactor,Nanyang Normal University,Nanyang Henan 473061,China
医药卫生
弥漫性大B细胞淋巴瘤肠道菌群血浆代谢物孟德尔随机化中介分析
diffuse large B-cell lymphomagut microbiotaplasma metabolitesMendelian randomizationmedi-ation analysis
《南阳师范学院学报》 2026 (1)
60-69,10
河南省科技厅重点研发项目"基于气血理论的益气活血法促缺血型烟雾病术后血管新生作用"(231111310900).
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