Conjugated bile acids are depleted during hypertension, nutritional rescue of which lowers blood pressure

Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown. To address this, we analyzed bile acid profiles of both human and hypertensive rat models and report that conjugated bile acids are inversely correlated with blood pressure in humans and rats. Notably, intervening with taurine rescued bile acid conjugation and reduced blood pressure in hypertensive rats. Subsequently, untargeted metabolomics uncovered lower energy metabolism following conjugation of bile acids as a mechanism alleviating high blood pressure. Together, this work reveals conjugated bile acids as nutritionally re-programmable anti-hypertensive metabolites.高血压是影响全球死亡率的首要危险因素。尽管已有临床可用的治疗药物，但未得到有效控制的高血压病例仍呈上升趋势，因此亟需开发新型且可持续的治疗方案。鉴于肠道菌群（gut microbiota）现已被证实是血压调控中的重要环节，靶向肠-肝轴（gut-liver axis）便是其中一条新兴研究路径——该轴内的代谢物可通过宿主与菌群的相互作用完成代谢交换。目前学界对于肠-肝轴内究竟哪些代谢物能够调控血压仍知之甚少。为解决这一科学问题，本研究分析了人类及高血压大鼠模型的胆汁酸（bile acid）谱，发现结合型胆汁酸（conjugated bile acids）在人类和大鼠体内均与血压呈负相关。值得注意的是，通过补充牛磺酸（taurine）可恢复胆汁酸结合过程，并降低高血压大鼠的血压水平。随后，非靶向代谢组学（untargeted metabolomics）分析揭示，胆汁酸结合反应伴随的能量代谢下调是缓解高血压的潜在机制。综上，本研究揭示结合型胆汁酸是一类可通过营养干预实现重编程的抗高血压代谢物。