The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
J Cell Mol Med. 2009 Aug;13(8B):2261-2270. doi: 10.1111/j.1582-4934.2009.00686.x. Epub 2009 Feb 4.
Probiotics are live non-pathogenic commensal organisms that exert therapeutic effects in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease. Little is known about mechanisms of action of commensal bacteria on intestinal motility and motility-induced pain. It has been proposed that probiotics affect intestinal nerve function, but direct evidence for this has thus far been lacking. We hypothesized that probiotic effects might be mediated by actions on colonic intrinsic sensory neurons. We first determined whether sensory neurons were present in rat colon by their responses to chemical mucosal stimulation and identified them in terms of physiological phenotype and soma morphotype. Enteric neuron excitability and ion channel activity were measured using patch clamp recordings. We fed 10(9)Lactobacillus reuteri (LR) or vehicle control to rats for 9 days. LR ingestion increased excitability (threshold for evoking action potentials) and number of action potentials per depolarizing pulse, decreased calcium-dependent potassium channel (IK(Ca)) opening and decreased the slow afterhyperpolarization (sAHP) in sensory AH neurons, similar to the IK(Ca) antagonists Tram-34 and clotrimazole. LR did not affect threshold for action potential generation in S neurons. Our results demonstrate that LR targets an ion channel in enteric sensory nerves through which LR may affect gut motility and pain perception.
益生菌是活的非致病性共生生物，在旅行者腹泻、肠易激综合征和炎症性肠病中发挥治疗作用。关于共生菌对肠道运动和运动引起的疼痛的作用机制知之甚少。有人提出益生菌可能会影响肠道神经功能，但到目前为止还缺乏直接证据。我们假设益生菌的作用可能是通过对结肠固有感觉神经元的作用来介导的。我们首先通过其对化学黏膜刺激的反应来确定大鼠结肠中是否存在感觉神经元，并根据生理表型和体形态来识别它们。使用膜片钳记录来测量肠神经元的兴奋性和离子通道活性。我们用 10(9)个嗜酸乳杆菌（LR）或载体对照喂养大鼠 9 天。LR 摄入增加了感觉 AH 神经元的兴奋性（引发动作电位的阈值）和每个去极化脉冲的动作电位数量，降低了钙依赖性钾通道（IK（Ca））的开放，并降低了缓慢后超极化（sAHP），类似于 IK（Ca）拮抗剂 tram-34 和克霉唑。LR 不影响 S 神经元产生动作电位的阈值。我们的结果表明，LR 靶向肠感觉神经中的一种离子通道，LR 可能通过该通道影响肠道运动和疼痛感知。
