Leaky gut: mechanisms, measurement and clinical implications in humans

Leaky gut: mechanisms, measurement and clinical implications in humans
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DOI:
10.1136/gutjnl-2019-318427
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发表时间:
2019-08-01
期刊:
GUT
影响因子:
24.5
通讯作者:
Camilleri, Michael
Camilleri, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Camilleri, Michael

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这篇关于“漏肠”的评论的目的是为临床医生讨论肠屏障的组成部分,肠通透性的不同测量,它们在非炎症性“应激状态”的扰动和饮食因素治疗的影响。公共领域中关于“健康”或“泄漏”肠道的信息需要在认可饮食排除、用无刺激性食物(如发酵食品)替代或使用补充剂修复损伤之前进行确认。肠屏障包括表面粘液、上皮层和免疫防御。上皮通透性的增加是由于细胞旁转运、细胞凋亡或跨细胞通透性增加所致。屏障功能可以使用口服施用的探针分子在体内测试,或使用来自人的粘膜活检在体外测试,将来自大鼠或小鼠的结肠粘膜或细胞层暴露于来自人患者的结肠粘膜或粪便的提取物。肠屏障的评估需要在上皮层之外进行测量。“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)增加渗透性。饮食因素可以逆转“应激”障碍中的肠漏和粘膜损伤。而炎症或溃疡性肠道疾病导致肠漏,没有这样的疾病可以通过简单地正常化肠道屏障功能治愈。恢复屏障功能是否能改善胃肠道或全身性疾病的临床表现仍有待证实。临床医生应该意识到胃肠道疾病中屏障功能障碍的可能性,并将屏障作为未来治疗的目标。
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.