Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Department of Regional Medicine and Education, Asahikawa Medical University, Asahikawa, Japan.
Digestion. 2024;105(1):34-39. doi: 10.1159/000533275. Epub 2023 Sep 6.
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal symptoms, but its pathogenesis is not fully understood.
We have recently shown in rats that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve the intestinal barrier dysfunction, which is a major pathophysiology of IBS. We have additionally shown that the neuropeptides injected intracisternally induced a visceral antinociceptive action against colonic distension. Since it has been known that intestinal barrier dysfunction causes visceral hypersensitivity, the other main pathophysiology of IBS, the neuropeptides act centrally to reduce leaky gut, followed by improvement of visceral sensation, leading to therapeutic action on IBS. It has been recently reported that there is a bidirectional relationship between neuroinflammation in the brain and the pathophysiology of IBS. For example, activation of microglia in the brain causes visceral hypersensitivity. Accumulating evidence has suggested that orexin, ghrelin, or oxytocin could improve neuroinflammation in the CNS. All these results suggest that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve intestinal barrier function and visceral sensation and also induce a protective action against neuroinflammation in the brain.
We therefore speculated that orexin, ghrelin, or oxytocin in the brain possess dual actions, improvement of visceral sensation/leaky gut in the gut, and reduction of neuroinflammation in the brain, thereby inducing a therapeutic effect on IBS in a convergent manner.
肠易激综合征（IBS）是一种以慢性腹部症状为特征的功能性肠病，但发病机制尚不完全清楚。
我们最近在大鼠中表明，神经肽如食欲素、胃饥饿素和催产素在大脑中起作用，可改善肠屏障功能障碍，这是 IBS 的主要病理生理学基础。我们还表明，脑室内注射的神经肽可引起对结肠扩张的内脏镇痛作用。由于已知肠屏障功能障碍会导致内脏高敏感性，这是 IBS 的另一个主要病理生理学基础，因此神经肽在中枢发挥作用以减少肠漏，继而改善内脏感觉，从而对 IBS 产生治疗作用。最近有报道称，大脑中的神经炎症与 IBS 的病理生理学之间存在双向关系。例如，大脑中小胶质细胞的激活会导致内脏高敏感性。越来越多的证据表明，食欲素、胃饥饿素或催产素可以改善中枢神经系统的神经炎症。所有这些结果表明，食欲素、胃饥饿素和催产素等神经肽在大脑中起作用，可改善肠屏障功能和内脏感觉，并对大脑中的神经炎症产生保护作用。
因此，我们推测大脑中的食欲素、胃饥饿素或催产素具有双重作用，可改善肠道的内脏感觉/肠漏，并减少大脑中的神经炎症，从而以收敛的方式对 IBS 产生治疗作用。
