Response by Hashimoto et al to Letter Regarding Article "Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm".
Response by Hashimoto et al to Letter Regarding Article "Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm".
复制标题
Hashimoto 等人对有关文章“肠道微生物群对颅内动脉瘤形成的潜在影响”的信件的回应。
DOI：
10.1161/hypertensionaha.119.12980
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Lawton,MichaelT
中科院分区：
文献类型：
--
作者：
Hashimoto,Tomoki;Sato,Hiroki;Shikata,Fumiaki;Lawton,MichaelT
我们要感谢 Rabelo 等人对我们最近题为“肠道微生物群对颅内动脉瘤形成的潜在影响”的文章提出的富有洞察力的评论。 1 使用颅内动脉瘤动物模型，我们展示了肠道微生物群与颅内动脉瘤形成之间的潜在联系。我们采用口服抗生素治疗来消除肠道微生物群，这种方法已广泛用于研究肠道微生物群在各种疾病模型中的作用。 2-5 我们还进行了在诱发动脉瘤之前停止抗生素治疗的实验，试图排除抗生素治疗对动脉瘤形成可能产生的直接影响。我们的研究代表了第一项从机制上将微生物群与颅内动脉瘤的病理生理学联系起来的研究。正如 Rabelo 等人所讨论的，尽管我们的动脉瘤模型在组织学和表型上非常模仿人类颅内动脉瘤，但该模型与人类动脉瘤的相关性尚未完全确定。动物模型可能无法重现人类动脉瘤形成和破裂的所有过程。导致人类动脉瘤形成和破裂的确切机制尚未确定，因此很难开发理想的动物模型。在所有动物模型中，动脉瘤都是诱发的，但不是自发形成的。然而，我们的模型中的表型、神经系统症状和自发破裂的表现与人类动脉瘤非常相似。尽管如此，我们同意 Rabelo 等人的观点，认为需要在人类和动物中进行更多研究，以明确肠道微生物群在颅内动脉瘤病理生理学中的作用。肠道微生物群可能间接或直接促进颅内动脉瘤的发展。肠道微生物群可能调节全身和局部炎症反应，这两种反应在动脉瘤形成的发展中发挥着关键作用。一些细菌可能会迁移到血管或动脉瘤壁中，直接提供可能促进动脉瘤发展的炎症环境。尽管不是结论性的，但我们的结果通常表明肠道微生物群在动脉瘤形成中的直接作用。我们没有在小鼠动脉瘤组织中检测到细菌 DNA，但我们发现肠道微生物群的存在可以调节模型中脑动脉的炎症。正如 Rabelo 等人正确指出的那样，一些研究探讨了潜在的细菌迁移到血管和动脉瘤壁在颅内动脉瘤的发展、生长和破裂中的作用。不幸的是，我们的实验方案
We would like to thank Rabelo et al for insightful comments on our recent article titled “Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm.” 1 Using an animal model of intracranial aneurysm, we have shown the potential link between the gut microbiota and the formation of the intracranial aneurysm. We used the treatment with oral antibiotics to eliminate the gut microbiota—a method that has been widely used in studying the roles of gut microbiota in various disease models. 2–5 We have also conducted the experiment in which the antibiotic treatment was stopped before the induction of aneurysm in an attempt to rule out the possible direct effects of the antibiotic treatment on the formation of aneurysms. Our study represented the first study to mechanistically connect the microbiota and the pathophysiology of intracranial aneurysm. As Rabelo et al discussed, although our aneurysm model closely mimics human intracranial aneurysms histologically and phenotypically, the relevance of this model to human aneurysms is not fully established. Animal models might not recapitulate all of the processes that are involved in aneurysm formation and rupture in humans. The exact mechanisms that cause aneurysm formation and rupture in humans have not been identified, making it difficult to develop an ideal animal model. In all animal models, aneurysms are induced but are not spontaneously formed. However, the phenotype, neurological symptom, and presentation of spontaneous ruptures in our model closely mimic those of human aneurysms. Nevertheless, we agree with Rabelo et al on the importance of more studies in both humans and animal to firmly establish the role of the gut microbiota in the pathophysiology of intracranial aneurysm.The gut microbiota may contribute to the development of intracranial aneurysm indirectly or directly. The gut microbiota may modulate systemic and local inflammatory responses, both of which are suggested to play critical roles in the development of aneurysm formation. It is possible that some of the bacteria may transmigrate into the vascular or aneurysmal wall, directly providing the inflammatory milieu that may promote the development of aneurysms. Although not conclusive, our results generally point to the direct role of gut microbiota in aneurysm formation. We did not detect bacterial DNA in the mouse aneurysm tissues, but we found that the presence of gut microbiota modulates inflammation in the cerebral arteries in our model. As Rabelo et al rightly pointed out, several studies explored the roles of the potential bacterial migration into the vascular and aneurysmal walls in the development, growth, and rupture of the intracranial aneurysm. Unfortunately, our experimental protocol
影响因子：
4.1
作者：
Aboukais, Rabih;Loiez, Caroline;Lejeune, Jean-Paul
通讯作者：
Lejeune, Jean-Paul
影响因子：
29
作者：
Koeth RA;Levison BS;Culley MK;Buffa JA;Wang Z;Gregory JC;Org E;Wu Y;Li L;Smith JD;Tang WHW;DiDonato JA;Lusis AJ;Hazen SL
通讯作者：
Hazen SL
影响因子：
64.5
作者：
Rakoff-Nahoum, S;Paglino, J;Medzhitov, R
通讯作者：
Medzhitov, R