Fukui Hiroshi
Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan.
Inflamm Intest Dis. 2016 Oct;1(3):135-145. doi: 10.1159/000447252. Epub 2016 Jul 20.
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.
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.
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.
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易位，这可能在各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。
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均有肠道上皮屏障功能障碍及通透性增加的描述。大多数临床报告使用激发试验的通透性测定或循环细菌标志物（如内毒素）的测量来评估“肠漏”。通过激发试验评估的肠道通透性通常与上皮紧密连接蛋白的变化或循环内毒素水平有关。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，而在其他疾病中则包括各种肠外器官。肠道菌群失调与肠道屏障功能障碍的关系已逐渐明晰。
尽管尚未证实直接的因果关系，但所有临床和实验数据均表明肠道高通透性在各种疾病炎症变化中的重要性。肠道通透性增加是疾病预防和治疗的新靶点。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以恢复健康的微生物群有可能在未来这些疾病的管理中取得突破。
