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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=483809
• 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.

肠道充满了与宿主具有互利共生关系的微生物（共生体）。共生体参与维持肠道表面细胞的完整性，帮助吸收食物，并调节免疫系统。一些共生生物（益生菌）在被摄入后提供营养，促进正常的肠道蠕动，并且还可以减少宿主体内的炎症（如果存在）。越来越明显的是，这些微生物与其宿主之间的相互作用比以前想象的更加复杂，并且越来越多的证据表明一些共生体可以直接影响宿主神经系统。例如，某些特定的益生菌种类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动。益生菌甚至可能改变大脑活动，包括情绪和焦虑。共生信号如何直接传递到神经系统一直是个谜。我们现在发现了第一个证据，表明特定种类的产酸乳杆菌益生菌可以靶向单一类型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体如何与宿主神经系统的一部分进行对话提供了重要的线索。这是解开共生体如何与神经系统不同部分沟通的途径的必要的第一步。我们设计了一系列生理实验，将揭示微生物向感觉神经细胞发出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王国之间正常生理信号传导所涉及的步骤提供第一个详细描述。然后，这项工作将扩展到其他微生物物种和宿主神经系统的组成部分，以确定共生生态系统如何与宿主神经系统相互作用，以促进细菌与其宿主之间的稳态关系。