scholarly journals The Intestinal Barrier and Permeability

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 83
Author(s):  
Piero Portincasa ◽  
Leonilde Bonfrate ◽  
Mohamad Khalil ◽  
Maria De Angelis ◽  
Francesco Maria Calabrese ◽  
...  
Keyword(s):  
Liver Steatosis ◽  
External Environment ◽  
Intestinal Barrier ◽  
Leaky Gut ◽  
Gut Permeability ◽  
Nonalcoholic Fatty Liver ◽  
Selective Permeability ◽  
Mucin Layer ◽  
Functional Features

The largest surface of the human body exposed to the external environment is the gut. At this level, the intestinal barrier includes luminal microbes, the mucin layer, gastrointestinal motility and secretion, enterocytes, immune cells, gut vascular barrier, and liver barrier. A healthy intestinal barrier is characterized by the selective permeability of nutrients, metabolites, water, and bacterial products, and processes are governed by cellular, neural, immune, and hormonal factors. Disrupted gut permeability (leaky gut syndrome) can represent a predisposing or aggravating condition in obesity and the metabolically associated liver steatosis (nonalcoholic fatty liver disease, NAFLD). In what follows, we describe the morphological-functional features of the intestinal barrier, the role of major modifiers of the intestinal barrier, and discuss the recent evidence pointing to the key role of intestinal permeability in obesity/NAFLD.

scholarly journals The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target

2021 ◽  
Vol 22 (15) ◽  
pp. 8161
Author(s):  
Takaomi Kessoku ◽  
Takashi Kobayashi ◽  
Kosuke Tanaka ◽  
Atsushi Yamamoto ◽  
Kota Takahashi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Barrier Function ◽  
Fatty Liver Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Leaky Gut ◽  
Nonalcoholic Fatty Liver

The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10%–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides

2020 ◽  
Author(s):  
Elke M. Muntjewerff ◽  
Kechun Tang ◽  
Lisanne Lutter ◽  
Gustaf Christoffersson ◽  
Mara J.T. Nicolasen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Chromogranin A ◽  
Intestinal Barrier ◽  
Enteroendocrine Cells ◽  
Leaky Gut ◽  
Gut Permeability ◽  
Gut Barrier ◽  
Ultrastructural Studies ◽  
New Findings

AbstractBackground and AimsA ‘leaky’ gut barrier has been implicated in the initiation and progression of a multitude of diseases, e.g., inflammatory bowel disease, irritable bowel syndrome, celiac disease, and colorectal cancers. Here we asked how Chromogranin A (CgA), a major hormone produced by the enteroendocrine cells, and Catestatin (CST), the most abundant CgA-derived proteolytic peptide, affect the gut barrier.Methods and ResultsUltrastructural studies on the colons from Catestatin (CST: hCgA352-372) knockout (CST-KO) mice revealed (i) altered morphology of tight (TJ) and adherens (AJ) junctions and desmosomes, indicative of junctional stress and (ii) an increased infiltration of immune cells compared to controls. Flow cytometry studies confirmed these cells to be macrophages and CD4+ T cells. Gene expression studies confirmed that multiple TJ-markers were reduced, with concomitant compensatory elevation of AJ and desmosome markers. Consistently, the levels of plasma FITC-dextran were elevated in the CST-KO mice, confirming leakiness’ of the gut. Leaky gut in CST-KO mice correlated with inflammation and a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in a multitude of diseases. Supplementation of CST-KO mice with recombinant CST reversed this leakiness and key phenotypes. Supplementation of CgA-KO mice with either CST alone, or with the pro-inflammatory proteolytic CgA fragment pancreastatin (PST: CgA250-301) showed that gut permeability is regulated by the antagonistic roles of these two peptide hormones: CST reduces and PST increases leakiness.ConclusionWe conclude that the enteroendocrine cell-derived hormone, CgA regulates gut permeability. CST is both necessary and sufficient to reduce the leakiness. CST acts primarily via antagonizing the effects of PST.What you need to knowBackground and ContextThe intestinal barrier is disrupted in many intestinal diseases such as Crohn’s disease. Chromogranin A (CgA) is produced by enteroendocrine cells in the gut. CgA is proteolytically cleaved into bioactive peptides including catestatin (CST) and pancreastatin (PST). The role of CgA in the gut is unknown.New findingsCgA is efficiently processed to CST in the gut and this processing might be decreased during active Crohn’s disease. CST promotes epithelial barrier function and reduces inflammation by counteracting PST.LimitationsThe complete mechanism of intestinal barrier regulation by CST likely involves a complex interplay between the enteroendocrine system, metabolism, the epithelium, the immune system and the gut microbiota.ImpactOur findings indicate that CST is a key modulator of the intestinal barrier and immune functions that correlates with disease severity of Crohn’s disease. CST could be a target for therapeutic interventions in Crohn’s disease.

scholarly journals Predictive Role of Interleukin-18 in Liver Steatosis in Obese Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Marta Flisiak-Jackiewicz ◽  
Anna Bobrus-Chociej ◽  
Eugeniusz Tarasów ◽  
Małgorzata Wojtkowska ◽  
Irena Białokoz-Kalinowska ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Liver Steatosis ◽  
Elevated Serum ◽  
Interleukin 18 ◽  
Obese Children ◽  
Proton Spectroscopy ◽  
Nonalcoholic Fatty Liver ◽  
Predictive Role ◽  
Intrahepatic Lipid

Introduction. Interleukin-18 (IL-18) is a proinflammatory cytokine associated with metabolic syndrome (MS). Nonalcoholic fatty liver disease (NAFLD) can be recognized as a feature of MS.Material and Methods. Serum IL-18 concentration was evaluated in serum of 108 obese children, determined with ELISA, and referred to degree of liver steatosis in USG or total intrahepatic lipid content assessed by magnetic resonance proton spectroscopy (1HMRS).Results. Fatty liver was confirmed in 89 children with USG and in 72 with1HMRS. IL-18 concentration demonstrated significantly higher values in patients than in controls. Significant correlations between IL-18 and ALT, GGT, triglycerides, hsCRP, and the degree of liver steatosis were demonstrated. NAFLD children had significantly higher level of IL-18, ALT, GGT, HOMA-IR, waist circumference, and total lipids content in1HMRS than other obese children. IL-18 level was also significantly higher in obese children with advanced liver steatosis. Measurement of serum IL-18 showed ability to differentiate children with fatty liver from those without steatosis.Conclusion. Elevated serum IL-18 concentration and its correlation with hepatocyte injury, systemic inflammation, and degree of liver steatosis support role in NAFLD pathomechanism. IL-18 can be considered to play a role in predicting advanced liver steatosis and fatty liver in obese children.

scholarly journals The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity

2021 ◽  
Vol 22 (21) ◽  
pp. 11359
Author(s):  
Paweł Serek ◽  
Monika Oleksy-Wawrzyniak
Keyword(s):  
Bacterial Infections ◽  
Intestinal Barrier ◽  
The Body ◽  
Entire Body ◽  
Gut Barrier ◽  
Selective Permeability ◽  
Current State ◽  
Viable Approach ◽  
Systemic Infections

The intestinal barrier plays an extremely important role in maintaining the immune homeostasis of the gut and the entire body. It is made up of an intricate system of cells, mucus and intestinal microbiota. A complex system of proteins allows the selective permeability of elements that are safe and necessary for the proper nutrition of the body. Disturbances in the tightness of this barrier result in the penetration of toxins and other harmful antigens into the system. Such events lead to various digestive tract dysfunctions, systemic infections, food intolerances and autoimmune diseases. Pathogenic and probiotic bacteria, and the compounds they secrete, undoubtedly affect the properties of the intestinal barrier. The discovery of zonulin, a protein with tight junction regulatory activity in the epithelia, sheds new light on the understanding of the role of the gut barrier in promoting health, as well as the formation of diseases. Coincidentally, there is an increasing number of reports on treatment methods that target gut microbiota, which suggests that the prevention of gut-barrier defects may be a viable approach for improving the condition of COVID-19 patients. Various bacteria–intestinal barrier interactions are the subject of this review, aiming to show the current state of knowledge on this topic and its potential therapeutic applications.

scholarly journals A New Look at the Pathogenesis and Possibilities of Treatment and Prevention of Autoimmune Diseases with the Role of the Intestinal Barrier and Increased Intestinal Permeability

2021 ◽  
Vol 17 (4) ◽  
pp. 82-88
Author(s):  
T.V. Kostoglod ◽  
◽  
T.S. Krolevets ◽  
M.A. Livzan
Keyword(s):  
Autoimmune Diseases ◽  
Intestinal Permeability ◽  
Lupus Erythematosus ◽  
Intestinal Barrier ◽  
Leaky Gut ◽  
Treatment And Prevention ◽  
Inflammatory Bowel ◽  
The Relationship

We described components of the intestinal barrier that maintains to integrity and assess their contribution and development of leaky gut syndrome. The relationship between intestinal permeability syndrome and excessive bacterial translocation with autoimmune diseases such as celiac disease, inflammatory bowel disease, type 1 diabetes mellitus, autoimmune hepatitis, and systemic lupus erythematosus were analyzed. The reasons for the occurrence of this syndrome were considered, its importance in the occurrence of these diseases, as well as in the development of therapeutic and preventive measures, was determined.

scholarly journals Endotoxins and Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Takaomi Kessoku ◽  
Takashi Kobayashi ◽  
Kento Imajo ◽  
Kosuke Tanaka ◽  
Atsushi Yamamoto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Liver Damage ◽  
Fatty Liver Disease ◽  
Controlled Trial ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Leaky Gut ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10–20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.

scholarly journals Evaluation of Biomarkers of NAFLD in a Cohort of Morbidly Obese Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Julia Kälsch ◽  
Lars P. Bechmann ◽  
Hagen Kälsch ◽  
Martin Schlattjan ◽  
Jochen Erhard ◽  
...  
Keyword(s):  
Liver Steatosis ◽  
Tunel Staining ◽  
Morbidly Obese ◽  
Surrogate Markers ◽  
Obese Patients ◽  
Review Of The Literature ◽  
Hepatocyte Apoptosis ◽  
Nonalcoholic Fatty Liver ◽  
Sirius Red

Hepatocyte apoptosis is a key event in nonalcoholic fatty liver disease (NAFLD), and serum apoptotic markers are emerging as surrogate markers for NAFLD. We studied the role of caspase-cleaved cytokeratin18 in the diagnosis of fibrosis in a cohort of 127 morbidly obese patients and also performed a review of the literature biomarkers of NAFLD and fibrosis. Here, we found that cleaved caspase 18 correlated with liver steatosis and liver injury as assessed by serum transaminase levels. Furthermore, hepatocyte apoptosis as assessed by cleaved CK18 and TUNEL staining correlated with the extent of fibrosis as assessed by Sirius Red staining and serum hyaluronic acid. These results underscore the important role of hepatocyte apoptosis in the pathogenesis of fibrosis in NAFLD, which led to the utilization of surrogate markers for apoptosis in the noninvasive diagnosis of NAFLD. We furthermore reviewed current literature of biomarkers of NAFLD and fibrosis.

scholarly journals Targeting of Secretory Proteins as a Therapeutic Strategy for Treatment of Nonalcoholic Steatohepatitis (NASH)

2020 ◽  
Vol 21 (7) ◽  
pp. 2296
Author(s):  
Kyeongjin Kim ◽  
Kook Hwan Kim
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Secretory Protein ◽  
Secretory Proteins ◽  
Therapeutic Approaches ◽  
Nonalcoholic Fatty Liver

Nonalcoholic steatohepatitis (NASH) is defined as a progressive form of nonalcoholic fatty liver disease (NAFLD) and is a common chronic liver disease that causes significant worldwide morbidity and mortality, and has no approved pharmacotherapy. Nevertheless, growing understanding of the molecular mechanisms underlying the development and progression of NASH has suggested multiple potential therapeutic targets and strategies to treat this disease. Here, we review this progress, with emphasis on the functional role of secretory proteins in the development and progression of NASH, in addition to the change of expression of various secretory proteins in mouse NASH models and human NASH subjects. We also highlight secretory protein-based therapeutic approaches that influence obesity-associated insulin resistance, liver steatosis, inflammation, and fibrosis, as well as the gut–liver and adipose–liver axes in the treatment of NASH.

scholarly journals Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Mario Masarone ◽  
Valerio Rosato ◽  
Marcello Dallio ◽  
Antonietta Gerarda Gravina ◽  
Andrea Aglitti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Primary Role ◽  
Nonalcoholic Fatty Liver ◽  
Starting Point

Liver steatosis without alcohol consumption, namely, nonalcoholic fatty liver disease (NAFLD), is a common hepatic condition that encompasses a wide spectrum of presentations, ranging from simple accumulation of triglycerides in the hepatocytes without any liver damage to inflammation, necrosis, ballooning, and fibrosis (namely, nonalcoholic steatohepatitis) up to severe liver disease and eventually cirrhosis and/or hepatocellular carcinoma. The pathophysiology of fatty liver and its progression is influenced by multiple factors (environmental and genetics), in a “multiple parallel-hit model,” in which oxidative stress plays a very likely primary role as the starting point of the hepatic and extrahepatic damage. The aim of this review is to give a comprehensive insight on the present researches and findings on the role of oxidative stress mechanisms in the pathogenesis and pathophysiology of NAFLD. With this aim, we evaluated the available data in basic science and clinical studies in this field, reviewing the most recent works published on this topic.

Sign in / Sign up

Export Citation Format

Share Document