Gut Microbes:神奇!肠道菌群调节血压新机制竟是从肾脏中“异常”感受器诞生

2018-01-03 转化医学网 Yui,Juka

维持血压的平衡是一个复杂的构成,它由多种不同的机制共同控制。在前面我们发现:高盐饮食、高血压和肠道菌群之间有着紧密的联系。

维持血压的平衡是一个复杂的构成,它由多种不同的机制共同控制。在前面我们发现:高盐饮食、高血压和肠道菌群之间有着紧密的联系。

1篇Science、2篇Nature:肠道菌群一日3篇重磅研究,都说了啥?

而在最近,研究人员发现了肠道菌群和高血压之间还有这另外的联系:这种联系说出来你可能难以置信,因为这一次,这个联系是“嗅”出来的。

刊登在《Gut Microbes》上一篇题为“A novel SCFA receptor, the microbiota, and bloodpressure regulation”的文章,为我们详细的阐述了肠道菌群和高血压之间的联系。


1.奇怪的嗅觉感受器

几年前,当约翰·霍普金斯大学(Johns Hopkins University)生理学副教授Jennifer Pluznick在进行一项生理和感官系统的时,她发现在肾脏中竟然有一种气味感受器Olfr78,而这种嗅觉感受器一般存在于鼻子内。

由于肾脏的功能是将排泄物从尿液中过滤,保持人体正常所需的渗透压,所以Pluznick对这个气味感受器的出现感到十分的讶异。

然而,当她深入研究嗅觉感受器时,Pluznick得出了一个惊人的结论!

2.“气味感受器”是“嗅”肠道菌群的

Pluznick的研究团队发现:肾脏中的气味感受器是“嗅”肠道菌群的。

在过去的几年里,Pluznick和她的团队一直致力于描述肠内微生物与肾脏是如何沟通的。他们发现肠道菌群和血压之间是存在联系的,因为肠道菌群被破坏的时候,血压调节接机制也会受损。

在肾脏中发现的这种嗅觉感受器叫做Olfr78,最初它在鼻子的感觉组织中被发现过,但是没有人知道它对何种特定的气味或化学元素有反应。

Pluznick在发现肾脏中有这种神奇的嗅觉感受器存在的时候,就开始对它进行各种各样的化学物质反应,最终发现Olfr78主要响应醋酸酯和丙酸酯。

那么这些短链脂肪酸分子来自于哪里呢?

来自于我们经常吃的膳食纤维的发酵降解。人类、老鼠、老鼠和其他动物都不能消化纤维,但肠道菌群可以。

肠道菌群消化这些膳食纤维并将99%的醋酸盐和丙酸盐释放到血液中,从而激活olfr78。研究发现任何机体本身对olfr78的调节作用都非常小,只有肠道菌群才是激活olfr78的唯一有效来源,而进一步的实验表明,这与调节血压有关。

3.肠道菌群控制血压的“两架马车”

人体不断地向血液中注入营养物质和化学信号来实现内环境稳态。而机体发挥这种控制作用的方法是使用一种叫做肾素的激素,当需要升高血压时,肾素会使血管变窄。Pluznick和她的同事发现,Olfr78会帮助推动了肾素的产生。


那么嗅觉感受器是如何继承这项工作的呢?

当研究人员进一步研究的时候,发现了肠道菌群调节血压的另一辆马车:Gpr41。

在去年的一篇论文中,Pluznick的研究生Niranjana Natarajan,现在是哈佛大学的博士后研究员,就揭示了Gpr41在血管内壁上的作用。与Olfr78一样,Gpr41也可以对醋酸酯和丙酮有反应,但它能降低血压而不是提高血压。

此外,Gpr41可以在低水平的醋酸酯和丙酸中反应,而Olfr78只在较高的水平上起作用。

于是一个完整的循环构成。

当吃饭摄入膳食纤维接触肠道时,肠道菌群以此为食并释放它们的脂肪酸信号。当所有被消耗的营养物质充斥在血液循环中时,这种脂肪酸信号就会激活降低血压的Gpr41。

例如,如果你在感恩节晚餐时持续吃一片马铃薯泥做成的派,那么gpr41就会释放自己甚至可能会把血压降至危险的水平。而这时Olfr78就会出现,Pluznick说。Olfr78随着下一波脂肪酸的到来而触发的,它通过刺激肾素收缩血管来防止血压下降。


芝加哥大学微生物组研究Jack Gilbert说道:“虽然关于微生物群落对健康的影响的说法近年来已变得司空见惯,但该领域应该不仅仅是简单地建立联系。”

人体总是处于一种动态平衡的过程,而在这个过程中反馈和负反馈调节机制必不可少。任何看起来多余的器官部分都留存在古老的生存智慧,肾脏中一个本不该存在的嗅觉感受器牵出来肠道菌群的血压调节机制,下次在其他器官发现不同寻常的组织呢?
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    2018-05-24 xjy02
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    2018-01-04 九九消寒

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    2018-01-03 九九消寒

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