State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
Nat Commun. 2020 Jun 25;11(1):3218. doi: 10.1038/s41467-020-16990-3.
Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.
未破裂颅内动脉瘤(UIA)是一种危及生命的脑血管疾病。肠道微生物组成的变化是否参与 UIA 的发生尚不清楚。我们在两个中国 UIA 患者和对照个体以及接受人供体粪便移植的小鼠队列中进行了病例对照宏基因组关联研究。粪便移植后,UIA 微生物群足以在小鼠中诱导 UIA。我们确定了与循环牛磺酸变化相关的 UIA 相关肠道微生物物种。具体而言,在人和小鼠中,Hungatella hathewayi 的丰度明显降低,与循环牛磺酸浓度呈正相关。一致地,灌胃 H. hathewayi 可使血清中的牛磺酸水平正常化,并防止小鼠颅内动脉瘤的形成和破裂。牛磺酸补充也可逆转颅内动脉瘤的进展。我们的研究结果为 H. hathewayi 相关牛磺酸耗竭作为 UIA 发病机制中的关键因素提供了新的见解。