Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Gut. 2019 Aug;68(8):1516-1526. doi: 10.1136/gutjnl-2019-318427. Epub 2019 May 10.
The objectives of this review on 'leaky gut' for clinicians are to discuss the components of the intestinal barrier, the diverse measurements of intestinal permeability, their perturbation in non-inflammatory 'stressed states' and the impact of treatment with dietary factors. Information on 'healthy' or 'leaky' gut in the public domain requires confirmation before endorsing dietary exclusions, replacement with non-irritating foods (such as fermented foods) or use of supplements to repair the damage. The intestinal barrier includes surface mucus, epithelial layer and immune defences. Epithelial permeability results from increased paracellular transport, apoptosis or transcellular permeability. Barrier function can be tested in vivo using orally administered probe molecules or in vitro using mucosal biopsies from humans, exposing the colonic mucosa from rats or mice or cell layers to extracts of colonic mucosa or stool from human patients. Assessment of intestinal barrier requires measurements beyond the epithelial layer. 'Stress' disorders such as endurance exercise, non-steroidal anti-inflammatory drugs administration, pregnancy and surfactants (such as bile acids and dietary factors such as emulsifiers) increase permeability. Dietary factors can reverse intestinal leakiness and mucosal damage in the 'stress' disorders. Whereas inflammatory or ulcerating intestinal diseases result in leaky gut, no such disease can be cured by simply normalising intestinal barrier function. It is still unproven that restoring barrier function can ameliorate clinical manifestations in GI or systemic diseases. Clinicians should be aware of the potential of barrier dysfunction in GI diseases and of the barrier as a target for future therapy.
本综述的目的是为临床医生讨论肠道屏障的组成部分、肠道通透性的多种测量方法、非炎症性“应激状态”下的通透性变化以及饮食因素治疗的影响。在认可饮食排除、用无刺激性食物(如发酵食品)替代或使用补充剂来修复损伤之前,需要对公众对“健康”或“渗漏”肠道的信息进行确认。肠道屏障包括表面黏液、上皮层和免疫防御。上皮通透性是由于细胞旁转运增加、细胞凋亡或细胞通透性增加而导致的。可以通过口服探针分子在体内或通过从人类获取粘膜活检、暴露大鼠或小鼠的结肠粘膜或细胞层来从人类患者的结肠粘膜或粪便提取物中进行体外测试来测试屏障功能。肠道屏障的评估需要超出上皮层的测量。应激障碍,如耐力运动、非甾体抗炎药给药、妊娠和表面活性剂(如胆汁酸和饮食因素,如乳化剂)会增加通透性。饮食因素可以逆转应激障碍中的肠道通透性和粘膜损伤。虽然炎症或溃疡性肠道疾病会导致肠道渗漏,但简单地使肠道屏障功能正常化并不能治愈此类疾病。恢复屏障功能是否可以改善胃肠道或全身性疾病的临床表现仍未得到证实。临床医生应该意识到胃肠道疾病中屏障功能障碍的潜在可能性,以及将屏障作为未来治疗的目标。
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