Gut commensal to enteric neuron communication: how ingstion of a lactobacillus species modulates intrinsic sensory neuron excitability and potassium ion channel properties

肠道共生肠神经元通讯：摄入乳酸菌如何调节内在感觉神经元兴奋性和钾离子通道特性

• 批准号: 371955-2009
• 负责人: Kunze, Wolfgang
• 金额: $ 1.75万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=435040
• 关键词: Gut; commensal; enteric; neuron; communication

The intestine is filled with microorganisms (commensals) that have mutually beneficial symbiotic relationship with their host. Commensals are involved in maintaining the integrity of the cells lining the gut surface, aiding in absorption of foodstuffs, and conditioning the immune system. Some commensal organisms, when ingested (probiotics) provide nutrients, facilitate normal intestinal motility, and may also reduce inflammation in the host if present. It is becoming evident that the interaction between these microorganisms and their hosts is more complex than previously thought and evidence is being accumulated that some commensals can affect directly the host nervous system. For example certain specific probiotic species alter autonomic nerve reflexes, the activity of nerve fibres connecting the intestine with the central nervous system. Probiotics may even alter brain activity including mood and anxiety. How the commensal signal directly to the nervous system has been a mystery. We have now found the 1st evidence that a particular species of acid producing Lactobacillus probiotic can target the activity of an ion channel molecule in a single type of intestinal sensory nerve cell. This surprising discovery provides a significant lead to the understanding of how certain commensals could talk to a part of the host nervous system; a necessary 1st step in unraveling the paths of how commensals communicate with different parts of the nervous system. We have designed a series of physiological experiments that will uncover the routes and molecular chemical mechanisms by which the microorganism signals to those sensory nerve cells. The results from these experiments will provide the 1st detailed description for the steps involved into normal physiological signaling between the bacterial and animal Kingdom. This work will then be expanded to involve other microbe species and components of the host nervous system to determine how the commensal ecosystem interacts with the host nervous system to facilitate a homeostatic relationship between the bacteria and their hosts.

肠道充满了与宿主有互惠共生关系的微生物（共生）。 Cormensals参与了维持肠道表面内壁的细胞的完整性，有助于吸收食物并调理免疫系统。摄取（益生菌）提供营养时，一些共生生物会促进正常的肠运动，如果存在，也可能减少宿主的炎症。显而易见的是，这些微生物及其宿主之间的相互作用比以前认为的更为复杂，并且积累了一些证据表明某些共性会直接影响宿主神经系统。例如，某些特定的益生菌会改变自主神经反射，即连接肠道与中枢神经系统的神经纤维的活性。益生菌甚至可能会改变大脑活动，包括情绪和焦虑。直接与神经系统的共生信号是一个谜。现在，我们发现了第一个证据表明，一种特定的产生乳杆菌的益生菌可以靶向单一类型的肠道感觉神经细胞中离子通道分子的活性。这一令人惊讶的发现为理解某些共生如何与宿主神经系统的一部分交谈的理解提供了重大的理解。揭开Comensals如何与神经系统不同部位沟通的路径的必要第一步。我们设计了一系列的生理实验，这些实验将揭示微生物信号与这些感觉神经细胞信号的途径和分子化学机制。这些实验的结果将为细菌和动物界之间正常生理信号的步骤提供第一个详细描述。然后，这项工作将扩展到涉及其他微生物物种和宿主神经系统的成分，以确定共生生态系统如何与宿主神经系统相互作用，以促进细菌与宿主之间的稳态关系。