与产生低活性形式 VacA 的幽门螺杆菌菌株定植于人胃中相比，产生活性形式分泌毒素 VacA 的幽门螺杆菌菌株定植与消化性溃疡病和胃癌的风险增加相关。先前的研究表明，活性 s1m1 形式的 VacA 会导致细胞空泡化和线粒体功能障碍。在这项研究中，我们试图确定 VacA 中毒的细胞代谢后果。非靶向代谢组学分析显示，与对照细胞相比，VacA 处理的胃十二指肠细胞（AGS 和 AZ-521）中的数百种代谢物发生了显着改变。通路分析表明 VacA 引起牛磺酸和亚牛磺酸代谢的改变。用纯化的活性 s1m1 形式的 VacA（而非活性低下的 s2m1 或 Δ6-27 VacA 突变蛋白（膜通道形成缺陷））处理细胞，会导致细胞内牛磺酸和亚牛磺酸浓度降低。在组织培养基中补充牛磺酸或亚牛磺酸可保护 AZ-521 细胞免受 VacA 诱导的细胞死亡。在存在或不存在细胞外牛磺酸的情况下，对 VacA 处理的 AZ-521 细胞或 AGS 细胞进行的非靶向整体代谢组学表明，牛磺酸是主要的细胞内代谢物，细胞外牛磺酸的补充会显着改变。这些结果表明，VacA 会引起细胞牛磺酸代谢的改变，并且牛磺酸的补充足以减弱 VacA 诱导的细胞死亡。我们在之前的文献中讨论了这些结果，这些文献显示了牛磺酸在细胞生理学和病理生理学或多种病理状况的治疗中的重要作用，包括胃溃疡、心血管疾病、恶性肿瘤、炎症性疾病和其他与衰老相关的疾病。

Colonization of the human stomach with Helicobacter pylori strains producing active forms of the secreted toxin VacA is associated with an increased risk of peptic ulcer disease and gastric cancer, compared with colonization with strains producing hypoactive forms of VacA. Previous studies have shown that active s1m1 forms of VacA cause cell vacuolation and mitochondrial dysfunction. In this study, we sought to define the cellular metabolic consequences of VacA intoxication. Untargeted metabolomic analyses revealed that several hundred metabolites were significantly altered in VacA-treated gastroduodenal cells (AGS and AZ-521) compared with control cells. Pathway analysis suggested that VacA caused alterations in taurine and hypotaurine metabolism. Treatment of cells with the purified active s1m1 form of VacA, but not hypoactive s2m1 or Δ6-27 VacA-mutant proteins (defective in membrane channel formation), caused reductions in intracellular taurine and hypotaurine concentrations. Supplementation of the tissue culture medium with taurine or hypotaurine protected AZ-521 cells against VacA-induced cell death. Untargeted global metabolomics of VacA-treated AZ-521 cells or AGS cells in the presence or absence of extracellular taurine showed that taurine was the main intracellular metabolite significantly altered by extracellular taurine supplementation. These results indicate that VacA causes alterations in cellular taurine metabolism and that repletion of taurine is sufficient to attenuate VacA-induced cell death. We discuss these results in the context of previous literature showing the important role of taurine in cell physiology and the pathophysiology or treatment of multiple pathologic conditions, including gastric ulcers, cardiovascular disease, malignancy, inflammatory diseases, and other aging-related disorders.