BACKGROUND Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal symptoms, but its pathogenesis is not fully understood. SUMMARY 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. KEY MESSAGES 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.

中文翻译：

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脑神经肽、神经炎症和肠易激综合症。

背景肠易激综合征（IBS）是一种以慢性腹部症状为特征的功能性肠病，但其发病机制尚不完全清楚。摘要 我们最近在大鼠身上发现，食欲素、生长素释放肽和催产素等神经肽在大脑中发挥作用，改善肠道屏障功能障碍，而肠道屏障功能障碍是 IBS 的主要病理生理学。我们还表明，脑池内注射的神经肽可诱导针对结肠扩张的内脏抗伤害作用。由于已知肠道屏障功能障碍会导致内脏过敏（IBS 的另一个主要病理生理学），因此神经肽的作用集中于减少肠漏，随后改善内脏感觉，从而对 IBS 产生治疗作用。最近有报道称，大脑神经炎症与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过敏。越来越多的证据表明，食欲素、生长素释放肽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、生长素释放肽和催产素等神经肽在大脑中发挥作用，改善肠道屏障功能和内脏感觉，并诱导针对大脑神经炎症的保护作用。关键信息因此，我们推测大脑中的食欲素、生长素释放肽或催产素具有双重作用，改善肠道内的内脏感觉/漏肠，并减少大脑中的神经炎症，从而以收敛的方式诱导对 IBS 的治疗作用。