Mediavilla Cristina
Department of Psychobiology, and Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Spain.
Neurochem Int. 2020 Dec;141:104882. doi: 10.1016/j.neuint.2020.104882. Epub 2020 Oct 14.
It is increasingly evident that bidirectional gut-brain signaling provides a communication pathway that uses neural, hormonal, and immunological routes to regulate homeostatic mechanisms such as hunger/satiety as well as emotions and inflammation. Hence, disruption of the gut-brain axis can cause numerous pathophysiologies, including obesity and intestinal inflammatory diseases. One chemical mediator in the gut-brain axis is orexin-A, given that hypothalamic orexin-A affects gastrointestinal motility and secretion, and peripheral orexin in the intestinal mucosa can modulate brain functions, making possible an orexinergic gut-brain network. It has been proposed that orexin-A acts on this axis to regulate nutritional processes, such as short-term intake, gastric acid secretion, and motor activity associated with the cephalic phase of feeding. Orexin-A has also been related to stress systems and stress responses via the hypothalamic-pituitary-adrenal axis. Recent studies on the relationship of orexin with immune system-brain communications in an animal model of colitis suggested an immunomodulatory role for orexin-A in signaling and responding to infection by reducing the production of pro-inflammatory cytokines (e.g., tumor necrosis factor α, interleukin-6, and monocyte chemoattractant protein-1). These studies suggested that orexin administration might be of potential therapeutic value in irritable bowel syndrome or chronic intestinal inflammatory diseases, in which gastrointestinal symptoms frequently coexist with behavioral disorders, including loss of appetite, anxiety, depression, and sleeping disorders. Interventions in the orexinergic system have been proposed as a therapeutic approach to these diseases and for the treatment of chemotherapeutic drug-related hyperalgesia and fatigue in cancer patients.
越来越明显的是，肠道与大脑之间的双向信号传递提供了一条利用神经、激素和免疫途径来调节诸如饥饿/饱腹感以及情绪和炎症等稳态机制的通信通路。因此，肠-脑轴的破坏会导致多种病理生理状况，包括肥胖症和肠道炎症性疾病。肠-脑轴中的一种化学介质是食欲素-A，因为下丘脑食欲素-A会影响胃肠蠕动和分泌，并且肠道黏膜中的外周食欲素可以调节脑功能，从而形成一个食欲素能肠-脑网络。有人提出食欲素-A作用于该轴来调节营养过程，如短期摄入、胃酸分泌以及与进食头期相关的运动活动。食欲素-A还通过下丘脑-垂体-肾上腺轴与应激系统和应激反应有关。最近在结肠炎动物模型中关于食欲素与免疫系统-大脑通信关系的研究表明，食欲素-A在通过减少促炎细胞因子（如肿瘤坏死因子α、白细胞介素-6和单核细胞趋化蛋白-1）的产生来进行信号传导和应对感染方面具有免疫调节作用。这些研究表明，给予食欲素可能对肠易激综合征或慢性肠道炎症性疾病具有潜在治疗价值，在这些疾病中，胃肠道症状常常与行为障碍同时存在，包括食欲不振、焦虑、抑郁和睡眠障碍。对食欲素能系统的干预已被提议作为治疗这些疾病以及癌症患者化疗药物相关痛觉过敏和疲劳的一种治疗方法。
