肠道渗透性、伴有便秘的肠易激综合征以及钠-氢交换异构体 3 (NHE3) 的作用。

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY Clinical and Experimental Gastroenterology Pub Date : 2024-06-06 eCollection Date: 2024-01-01 DOI:10.2147/CEG.S455101
Brian E Lacy, David Rosenbaum, Susan Edelstein, Kenji Kozuka, Laura A Williams, David C Kunkel
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引用次数: 0

摘要

肠道通透性增加已被确定为与肠易激综合征(IBS)发病有关的众多病理生理因素之一,肠易激综合征是一种常见的肠道与大脑相互作用紊乱的疾病。肠道上皮细胞层的通透性是有限的,细胞旁通透性的量受到严格控制,以保证肠腔中离子、营养物质和水分的吸收。感染、食物中毒产生的毒素或过敏原等各种损伤都可能导致肠道对大分子的通透性增加,进而引起炎症反应,并与肠易激综合征患者的腹痛有关。这篇综述文章讨论了肠道渗透性增加在肠易激综合征(IBS)中的作用,通过一个病人的病例,重点讨论了伴有便秘的肠易激综合征(IBS-C),据报道该病人在与胃肠专科医生初次接触时就被诊断为 "肠漏综合征"。我们回顾了几种测量患者肠道通透性方法的优缺点,并讨论了在 IBS-C 患者的治疗过程中何时适合测量肠道通透性。此外,我们还讨论了通过抑制钠-氢交换异构体 3(NHE3)来改变细胞内 pH 值,从而将肠道屏障恢复到健康状态的可能机制。Tenapanor 是一种吸收率极低的 NHE3 小分子抑制剂,已被美国食品药品管理局批准用于治疗成人肠易激综合征。临床前研究表明,替那帕诺可通过抑制 NHE3 影响紧密连接蛋白的构象,阻止肠腔内大分子的旁细胞转运,从而恢复 IBS-C 的肠道屏障。对有腹痛症状的 IBS-C 患者进行通透性增加测试,有助于为治疗方法的选择提供依据,并改变患者对 "肠漏综合征 "的误解。
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Intestinal Permeability, Irritable Bowel Syndrome with Constipation, and the Role of Sodium-Hydrogen Exchanger Isoform 3 (NHE3).

Increased intestinal permeability has been identified as one of the many pathophysiological factors associated with the development of irritable bowel syndrome (IBS), a common disorder of gut-brain interaction. The layer of epithelial cells that lines the intestine is permeable to a limited degree, and the amount of paracellular permeability is tightly controlled to enable the absorption of ions, nutrients, and water from the lumen. Increased intestinal permeability to macromolecules can be triggered by a variety of insults, including infections, toxins from food poisoning, or allergens, which in turn cause an inflammatory response and are associated with abdominal pain in patients with IBS. This review article discusses increased intestinal permeability in IBS, focusing on IBS with constipation (IBS-C) through the lens of a patient case with a reported prior diagnosis of "leaky gut syndrome" upon initial contact with a gastrointestinal specialist. We review advantages and disadvantages of several methods of measuring intestinal permeability in patients and discuss when measuring intestinal permeability is appropriate in the therapeutic journey of patients with IBS-C. Furthermore, we discuss a possible mechanism of restoring the intestinal barrier to its healthy state through altering intracellular pH by inhibiting sodium-hydrogen exchanger isoform 3 (NHE3). Tenapanor is a minimally absorbed, small-molecule inhibitor of NHE3 that has been approved by the US Food and Drug Administration for the treatment of IBS-C in adults. Preclinical studies showed that tenapanor may restore the intestinal barrier in IBS-C by affecting the conformation of tight junction proteins via NHE3 inhibition to block the paracellular transport of macromolecules from the intestinal lumen. Testing for increased permeability in patients with IBS-C who experience abdominal pain may help inform the choice of therapeutics and alter patients' misconceptions about "leaky gut syndrome".

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来源期刊
Clinical and Experimental Gastroenterology
Clinical and Experimental Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
5.10
自引率
0.00%
发文量
26
审稿时长
16 weeks
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