Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?
Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?
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DOI：
10.1159/000447252
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发表时间：
2016-10-01
影响因子：
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通讯作者：
Fukui, Hiroshi
中科院分区：
文献类型：
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作者：
Fukui, Hiroshi
背景：由于屏障功能障碍导致的肠道通透性增加被认为会引起微生物移位，这可能在多种疾病中诱发低度炎症。然而，这一系列事件尚未得到全面评估。
总结：在炎症性肠病（IBD）、肠易激综合征（IBS）、酒精性肝病、非酒精性脂肪性肝炎（NASH）、肝硬化、急性胰腺炎、原发性胆汁性胆管炎（PBC）、1型和2型糖尿病、慢性肾脏病、慢性心力衰竭（CHF）、抑郁症及其他疾病患者中，已描述了肠道上皮屏障功能障碍和通透性增加。大多数临床报告要么使用激发试验的通透性检测，要么测量循环细菌标志物如内毒素来评估“肠漏”。通过激发试验评估的肠道通透性常常与上皮中紧密连接蛋白的变化或循环内毒素水平相关。在IBD、酒精性肝病、NASH、肝硬化、PBC、梗阻性黄疸、重症急性胰腺炎和CHF患者中，除了通透性增加外，还发现了内毒素血症和促炎细胞因子血症。在IBS和抑郁症患者的血清中，分别检测到抗鞭毛蛋白抗体和抗脂质A抗体，同时伴有通透性增加和促炎细胞因子血症。感染部位在IBD和IBS中局限于肠道，在其他疾病中包括各种肠外器官。肠道菌群失调与肠道屏障功能障碍的关系已逐渐明确。
关键信息：尽管尚未确认直接的因果关系，但所有临床和实验数据都表明肠道高通透性在多种疾病的炎症变化中具有重要性。肠道通透性增加是疾病预防和治疗的一个新靶点。考虑到“肠漏”和肠道菌群失调与主要疾病的密切关系，我们可以得出结论，精心的饮食和益生菌方法来恢复健康的微生物群有可能在未来这些疾病的治疗中取得突破。
BACKGROUND: Increased intestinal permeability due to barrier dysfunction is supposed to cause microbial translocation which may induce low-grade inflammation in various diseases. However, this series of events has not been comprehensively evaluated yet.SUMMARY: Intestinal epithelial barrier dysfunction and increased permeability have been described in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), alcoholic liver disease, nonalcoholic steatohepatitis (NASH), liver cirrhosis, acute pancreatitis, primary biliary cholangitis (PBC), type 1 and type 2 diabetes, chronic kidney disease, chronic heart failure (CHF), depression, and other diseases. Most clinical reports used either permeability assays of challenge tests or measurement of circulating bacterial markers like endotoxin for assessment of 'the leaky gut'. The intestinal permeability assessed by the challenge tests has often been related to the changes of tight junction proteins in the epithelium or circulating endotoxin levels. In patients with IBD, alcoholic liver disease, NASH, liver cirrhosis, PBC, obstructive jaundice, severe acute pancreatitis, and CHF, endotoxemia and proinflammatory cytokinemia have been found in addition to increased permeability. In the serum of patients with IBS and depression, antiflagellin antibodies and antilipid A antibodies were detected, respectively, together with increased permeability and proinflammatory cytokinemia. The site of infection, which is localized to the intestine in IBD and IBS, includes various extraintestinal organs in other diseases. The relation of gut dysbiosis to intestinal barrier dysfunction has gradually been clarified.KEY MESSAGES: Although no direct cause-and-effect relationship has been confirmed, all clinical and experimental data suggest the importance of intestinal hyperpermeability in the inflammatory changes of various diseases. Increased intestinal permeability is a new target for disease prevention and therapy. Considering the close relationship of 'the leaky gut' and gut dysbiosis to the major diseases, we can conclude that meticulous dietetic and probiotic approaches to recover healthy microbiota have the potential to make a breakthrough in the management of these diseases tomorrow.