Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?

Abstract

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.

Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction

“…Dietary assessment studies have shown that PACs, especially procyanidins, are among the most abundant polyphenols in the human diet [6], as they are present in a variety of botanical sources and plant food products such as tea, fruits, nuts, cacao products, legumes, and cereal grains [1,2]. However, PAC intake varies widely between geographical regions and cultures and is greatly dependent on eating habits, lifestyle behaviors, and socioeconomic status [78].…”

“…When there are disturbances in the barrier function and mucosal immune homeostasis, the influx of intestine luminal content triggers an exaggerated mucosal immune response [1]. Ultimately, chronic exposition to these detrimental environmental stimuli may lead to the development of local and systemic inflammatory conditions [2,3].…”

The Evolving Role of Gut Microbiota in the Management of Irritable Bowel Syndrome: An Overview of the Current Knowledge

“…In IBS patients, GI dysbiosis has been associated with a visceral increased perception of pain and enhanced mucosal permeability that is provoked by the defective mucosal epithelial barrier, interfering with gut immune homeostasis and subsequently promoting gut inflammation and enhancing cellular and mucosal immune activation [28,29]. Moreover, it has also been associated with changing gut motility, low-grade chronic inflammation, alterations of the enteric nervous system, and vagal afferents neurons as well as brain functions [30][31][32].…”

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…Therefore, when these epithelial barriers break down, external toxins, allergens, and pollutants penetrate into the body, thereby inducing and accelerating inflammation for defense against them 1 2 . In addition, breakdown of epithelial barrier result in increased epithelial permeability, which allows internal leakage such as diarrhea and jaundice 3 …”