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，双向肠脑信号提供了一种交流通路，该通路使用神经、激素和免疫途径来调节稳态机制，如饥饿/饱腹感以及情绪和炎症。因此，肠脑轴的破坏会导致多种病理生理，包括肥胖和肠道炎症疾病。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影响胃肠道运动和分泌，而肠粘膜中的外周食欲素可以调节大脑功能，从而使食欲素能肠-脑网络成为可能。已经提出，orexin-A 作用于该轴以调节营养过程，例如短期摄入、胃酸分泌和与头侧进食相关的运动活动。通过下丘脑-垂体-肾上腺轴。最近对结肠炎动物模型中食欲素与免疫系统-大脑通讯关系的研究表明，食欲素-A 通过减少促炎细胞因子（例如，肿瘤坏死因子 α、白细胞介素 6 和单核细胞趋化蛋白 1）。这些研究表明，orexin 给药可能对肠易激综合征或慢性肠道炎症疾病具有潜在的治疗价值，其中胃肠道症状经常与行为障碍共存，包括食欲不振、焦虑、抑郁和睡眠障碍。