Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Division of HBP Surgery and Transplantation, Department of Surgery, St. Eloi Hospital, Montpellier University Hospital-School of Medicine, Montpellier, France.
Institut National de la Santé et de la Recherche Médicale (INSERM) U1223, Paris, France; Innate Immunity Unit, Institut Pasteur, Paris, France.
Pharmacol Res. 2020 Sep;159:104947. doi: 10.1016/j.phrs.2020.104947. Epub 2020 May 31.
Inflammatory bowel disease (IBD) refers to a group of heterogeneous disorders associated with chronic inflammation of the gut, having a high rate of incidence in the world. In the present review, we will discuss the link between the short-chain fatty acids, especially butyrate (BT), produced by bacterial fermentation of dietary fiber, and IBD development. Current knowledge supports an anti-inflammatory role for BT and suggests that BT insufficiency may be involved in the pathogenesis of IBD. We will present the molecular mechanisms involved in the anti-inflammatory effect of BT, namely histone deacetylase inhibitor activity, activation of PPARγ and of GPR109A, GPR41 and GPR43 receptors. The histone deacetylase inhibitor activity of BT depends of its absorption by colonocytes. Therefore, BT transporters are also important players in BT-induced anti-inflammatory effect at colonic level. Finally, BT-based future prospects for IBD therapy (modulation of diet (through increased prebiotic (fiber) ingestion) and microbiota (BT-producing probiotic bacteria) supplementation - that can increase the levels of BT in colon - and development of pharmacological BT analogues) will be presented.
炎症性肠病（IBD）是一组与肠道慢性炎症相关的异质性疾病，在世界范围内发病率较高。在本综述中，我们将讨论膳食纤维细菌发酵产生的短链脂肪酸（特别是丁酸盐（BT））与 IBD 发展之间的联系。目前的知识支持 BT 具有抗炎作用，并表明 BT 不足可能参与 IBD 的发病机制。我们将介绍 BT 抗炎作用涉及的分子机制，即组蛋白去乙酰化酶抑制剂活性、激活 PPARγ 和 GPR109A、GPR41 和 GPR43 受体。BT 的组蛋白去乙酰化酶抑制剂活性取决于其被结肠细胞吸收。因此，BT 转运体也是 BT 在结肠水平诱导抗炎作用的重要参与者。最后，将介绍基于 BT 的 IBD 治疗的未来前景（通过增加益生元（纤维）摄入和微生物群（产生 BT 的益生菌）补充来调节饮食 - 可以增加结肠中的 BT 水平 - 和开发药理 BT 类似物）。
