Shi Zhenyu, Zhao Chenyi, Yu Xiaowen, Zhao Dingding, Li Yongqiang
Huaihe Hospital, Henan University, Kaifeng, People's Republic of China.
Chongqing Key Laboratory of Traditional Chinese Medicine to Prevent and Treat Autoimmune Diseases, Chongqing, People's Republic of China.
AMB Express. 2025 Jun 14;15(1):92. doi: 10.1186/s13568-025-01901-w.
Tuberculosis (TB), caused by infectious agent Mycobacterium tuberculosis (Mtb) seriously poses a great threat to health. An array of metabolites generated by metabolic pathways are essential for Mtb pathophysiology. However, a specific causal relationship between TB and human metabolites remains indistinct. This study aimed to investigate the relationship between 1400 metabolites and TB by Mendelian randomization (MR) analysis. In this study, a total of 1400 metabolites were utilized as exposure factors, while TB-related data served as the outcomes. And TwoSampleMR package and R software were adopted to perform this MR analysis. Various regression fitting methods were employed to conduct MR analysis, including inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode. In addition, potential biases arising from linkage disequilibrium and weak instrumental variables were considered. Metabolites that failed to meet the criteria in both the heterogeneity and pleiotropy tests were considered to have no substantial causal influence on the results, ensuring the robustness and reliability of our analysis. IVW analysis showed that six human metabolites exhibited a significant causal influence (P < 0.05) on TB. Among them, dodecanedioate, myristoleate (14:1n5), and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE(p-16:0/20:4) demonstrated a strong causally positive effect on TB, indicating that with the increase of these metabolites, TB progressed robustly. Glycerol 3-phosphate, sphingomyelin (d18:1/20:2, d18:2/20:1, and d16:1/22:2), and 2-methylserine were significantly negatively associated with TB, an increase in these metabolites inhibited TB progression. This is the first time to reveal the causal effects of human metabolites on TB through MR, and the metabolites may be potential biomarkers candidate for TB diagnosis, and monitoring these metabolites might have great clinic significance for TB diagnosis and treatment in the future.
由传染性病原体结核分枝杆菌（Mtb）引起的结核病（TB）严重威胁着健康。代谢途径产生的一系列代谢产物对Mtb的病理生理学至关重要。然而，结核病与人类代谢产物之间的具体因果关系仍不明确。本研究旨在通过孟德尔随机化（MR）分析探讨1400种代谢产物与结核病之间的关系。在本研究中，总共1400种代谢产物被用作暴露因素，而结核病相关数据作为结果。采用TwoSampleMR软件包和R软件进行此项MR分析。采用了各种回归拟合方法进行MR分析，包括逆方差加权（IVW）、MR-Egger、加权中位数、简单模式和加权模式。此外，还考虑了连锁不平衡和弱工具变量产生的潜在偏差。在异质性和多效性检验中未符合标准的代谢产物被认为对结果没有实质性因果影响，从而确保了我们分析的稳健性和可靠性。IVW分析表明，六种人类代谢产物对结核病表现出显著的因果影响（P < 0.05）。其中，十二烷二酸、肉豆蔻油酸（14:1n5）和1-(1-烯基-棕榈酰基)-2-花生四烯酰基-GPE（p-16:0/20:4）对结核病表现出强烈的因果正效应，表明随着这些代谢产物的增加，结核病进展迅速。3-磷酸甘油、鞘磷脂（d18:1/20:2、d18:2/20:1和d16:1/22:2）和2-甲基丝氨酸与结核病显著负相关，这些代谢产物的增加抑制了结核病的进展。这是首次通过MR揭示人类代谢产物对结核病的因果效应，这些代谢产物可能是结核病诊断的潜在生物标志物候选物，监测这些代谢产物可能对未来结核病的诊断和治疗具有重要的临床意义。
