scholarly journals Host Factors in Dysregulation of the Gut Barrier Function during Alcohol-Associated Liver Disease

2021 ◽  
Vol 22 (23) ◽  
pp. 12687
Author(s):  
Luca Maccioni ◽  
Isabelle A. Leclercq ◽  
Bernd Schnabl ◽  
Peter Stärkel
Keyword(s):  
Liver Disease ◽  
Defense Mechanisms ◽  
Inflammatory Responses ◽  
Public Health Problem ◽  
Systemic Circulation ◽  
Decompensated Cirrhosis ◽  
Major Public Health Problem ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Gut Barrier Function

Chronic alcohol consumption and alcohol-associated liver disease (ALD) represent a major public health problem worldwide. Only a minority of patients with an alcohol-use disorder (AUD) develop severe forms of liver disease (e.g., steatohepatitis and fibrosis) and finally progress to the more advanced stages of ALD, such as severe alcohol-associated hepatitis and decompensated cirrhosis. Emerging evidence suggests that gut barrier dysfunction is multifactorial, implicating microbiota changes, alterations in the intestinal epithelium, and immune dysfunction. This failing gut barrier ultimately allows microbial antigens, microbes, and metabolites to translocate to the liver and into systemic circulation. Subsequent activation of immune and inflammatory responses contributes to liver disease progression. Here we review the literature about the disturbance of the different host defense mechanisms linked to gut barrier dysfunction, increased microbial translocation, and impairment of liver and systemic inflammatory responses in the different stages of ALD.

Targeting the gut-liver-immune axis to treat cirrhosis

Gut ◽  
2020 ◽  
pp. gutjnl-2020-320786 ◽  
Author(s):  
Thomas Henry Tranah ◽  
Lindsey A Edwards ◽  
Bernd Schnabl ◽  
Debbie Lindsay Shawcross
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bacterial Infections ◽  
Hepatorenal Syndrome ◽  
Intestinal Barrier ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Barrier Dysfunction ◽  
Bacterial Peritonitis ◽  
Gut Barrier Function

Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.

scholarly journals Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Xin Dai ◽  
Bangmao Wang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Barrier Function ◽  
Fatty Liver Disease ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Nonalcoholic Fatty Liver ◽  
Gut Barrier Function

Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of “gut-liver axis,” more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease.

scholarly journals Prevention of Gut Barrier Dysfunction During Acute Massive Blood Loss (Experimental Study)

2019 ◽  
Vol 15 (4) ◽  
pp. 76-87
Author(s):  
A. Y. Yakovlev ◽  
G. A. Boyarinov ◽  
D. V. Ryabikov ◽  
M. A. Ryabikova ◽  
D. M. Protasov ◽  
...  
Keyword(s):  
Blood Loss ◽  
Portal Vein ◽  
Mucous Membrane ◽  
Systemic Circulation ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Massive Blood Loss ◽  
Weight Growth ◽  
Series Of Experiments ◽  
Portal Veins

Purpose of the study: to investigate the influence of hypovolemia correction by infusion of malate-containing preparations and subsequent glutamine-enriched nutritional support on the maintenance of gut barrier and overhydration in animals with acute massive blood loss/  Materials and methods. Blood samples were harvested from the tail and portal veins of rats (n=100) at different time points after the acute blood loss (>30% V/V) . Bacterial blood cultures for growth, lipopolysaccharide and presepsin concentrations, colon structures and animal weight were analyzed in blood and plasma specimens 1 hour, one day and 3 days after the hypovolemia correction. To correct the hypovolemia, in the 1st series of experiments, the Ringer’s solution and standard nutrient mixture were used; in the 2nd series malatecontaining solution and standard nutrient mixture were administered; in the 3rd series a malate-containing solution and glutamine-enriched nutrient mixture were employed.Results. In the portal vein blood of intact animals, endotoxin measurement was equal to 17.8Ѓ}3.9 pg/ml, that of presepsin — 405.6Ѓ}80.1 pg/ml. At all stages, tail and portal blood bacterial cultures were negative demonstrating an absence of bacterial growth and gut barrier intactness for live microorganisms. One hour after hypovolemia correction and blood reinfusion, multifold increase in endotoxin concentration in the blood from both portal and tail veins was accompanied by significant increase of presepsin concentration. 24 hours after the blood loss, in the animals of the 2nd and 3rd series, the levels of endotoxin, presepsin, and edema of the colon mucous membrane and submucosal space has become lower than those in the 1st series. Three days later, the advantages of glutamine-containing nutrition in the 3rd series of the experiment were determined that revealed decreasing the endotoxin and presepsin concentrations in the portal and tail vein blood and diminishing the levels of interstitial edema of colon and animal weight growth.Conclusion. Administration of malate-containing infusion preparations and glutamine-enriched nutrition after an acute massive blood loss contributes to decreasing presepsin production in GIT organs, abrogating endotoxin translocation into the portal vein and systemic circulation, lessening severity of edema of the mucous membrane and submucosal space of the colon, and reducing the previously increased animal body mass.

scholarly journals Clinical Analysis of Gut Barrier Dysfunction in Patients with Advanced Colorectal Cancer Undergoing Cytoreductive Surgery and HIPEC

2021 ◽  
Author(s):  
Le lai Ping ◽  
Jiang xu Mian ◽  
Chen Wei
Keyword(s):  
Colorectal Cancer ◽  
Cytoreductive Surgery ◽  
Barrier Function ◽  
Intraperitoneal Injection ◽  
Advanced Colorectal Cancer ◽  
Patient Characteristics ◽  
Barrier Dysfunction ◽  
Large Area ◽  
Gut Barrier ◽  
Gut Barrier Function

Abstract Introduction: Hyperthermic intraperitoneal chemotherapy combinedwith cytoreductive surgery is a preferred treatment option for advanced colorectal cancer patients. However, little is known whether the HIPEC can cause the damage of gut barrier function.Methods: A total of 123 patients underwent surgical resection for advanced CRC. Sixty-five patients were treated HIPEC after cytoreductive surgery whereas 58 patients underwent surgery only. Gut barrier function were evaluated using the expression of serum DAO/D-la/ET on D1/D5/D10 after surgery. Both groups were compared for patient characteristics, perioperative data and gut barrier function. Moreover, rats received intraperitoneal injection of retetrexed to observe possible changes of colonic structure under optical microscope.Results: Both groups were comparable with respect to general patient characteristics and post-operative complications. The HIPEC+CRS group was associated with a higher postoperative serum level of DAO/D-la on D1/D5 (p < 0.05) and ET on D5 after surgery (p < 0.05) than that of the surgery only group. Ten days after surgery showed no statistical difference between the 2 groups (p > 0.05).A large area structure disorder, epithelial necrosis, glandular deformation and a large number of lymphocytes infiltration was found in the lamina propria in animals received intraperitoneal injection of retetrexed.Conclusion: In this study, CRS combined with HIPEC does have but only an irreversible impact on gut barrier for advanced CRC patients.

scholarly journals Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 367 ◽  
Author(s):  
Raoel Maan ◽  
Adriaan J. van der Meer
Keyword(s):  
Liver Disease ◽  
Treatment Options ◽  
Public Health Problem ◽  
Hcv Infection ◽  
New Drugs ◽  
European Medicines Agency ◽  
Major Public Health Problem ◽  
Advanced Liver Disease ◽  
Specific Patient ◽  
Chronic Hcv

Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.

A CASE OF PARAQUAT POISONING PRESENTING WITH MULTIORGAN DYSFUNCTION

2021 ◽  
pp. 59-60
Author(s):  
Venkata sai suhas Yadlapati ◽  
Nirmala Devi ◽  
V.R.Mohan Rao
Keyword(s):  
Public Health ◽  
Acute Kidney Injury ◽  
Developing Countries ◽  
Liver Disease ◽  
Early Diagnosis ◽  
Fatal Case ◽  
Case Fatality ◽  
Kidney Injury ◽  
Public Health Problem ◽  
Major Public Health Problem

Ÿ Self-poisoning with pesticides is a major public health problem in developing countries with an estimated 300 000 deaths each year.Very high case fatality (>50%) - due both to its inherent toxicity and the lack of early diagnosis and effective treatment.Though it is easily availabile, poisoning with this toxin is not common. Fatal dose of paraquat is so trivial that >10 ml poison can damage lungs permanently. Ÿ In this context we present a fatal case of 30 yr old male patient who have consumed paraquat and presented with extensive complication of acute kidney injury, and lung injury and liver disease.

scholarly journals Host-Microbe Interactions and Defense Mechanisms in the Development of Amoebic Liver Abscesses

2009 ◽  
Vol 22 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Julien Santi-Rocca ◽  
Marie-Christine Rigothier ◽  
Nancy Guillén
Keyword(s):  
Public Health ◽  
Stress Responses ◽  
Defense Mechanisms ◽  
Public Health Problem ◽  
Host Responses ◽  
Major Public Health Problem ◽  
Public Health Burden ◽  
Liver Abscesses ◽  
Host Microbe Interactions ◽  
Parasite Factors

SUMMARY Amoebiasis by Entamoeba histolytica is a major public health problem in developing countries and leads to several thousand deaths per year. The parasite invades the intestine (provoking diarrhea and dysentery) and the liver, where it forms abscesses (amoebic liver abscesses [ALAs]). The liver is the organ responsible for filtering blood coming from the intestinal tract, a task that implies a particular structure and immune features. Amoebae use the portal route and break through the sinusoidal endothelial barrier to reach the hepatic parenchyma. When faced with systemic and cell-mediated defenses, trophozoites adapt to their new environment and modulate host responses, leading to parasite survival and the formation of inflammatory foci. Cytopathogenic effects and the onset of inflammation may be caused by diffusible products originating from parasites and/or immune cells either by their secretion or by their release after cell death. Liver infection thus results from the interplay between E. histolytica and hepatic cells. Despite its importance in terms of public health burden, the lack of integrated data on ALA genesis means that we have only an incomplete description of the initiation and development of hepatic amoebiasis. Here, we review the main steps of ALA development as well as the responses triggered in both the host and the parasite. Transcriptome studies highlighted parasite factors involved in adherence to human cells, cytopathogenic effects, and adaptative and stress responses. An understanding of their role in ALA development will help to unravel the host-pathogen interactions and their evolution throughout the infection.

scholarly journals Genetically obese mice do not show increased gut permeability or faecal bile acid hydrophobicity

2013 ◽  
Vol 110 (6) ◽  
pp. 1157-1164 ◽  
Author(s):  
Lotta K. Stenman ◽  
Reetta Holma ◽  
Helena Gylling ◽  
Riitta Korpela
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Permeability ◽  
Low Grade ◽  
Obese Mice ◽  
Gut Permeability ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Genetic Obesity ◽  
Gut Barrier Function

Gut barrier dysfunction may lead to metabolic endotoxaemia and low-grade inflammation. Recent publications have demonstrated gut barrier dysfunction in obesity induced by a diet high in fat, and a pathogenetic role for luminal bile acids has been proposed. We aimed to investigate whether genetically obese mice develop increased gut permeability and alterations in luminal bile acids on a diet with a regular fat content. We used seven obese male ob/ob mice of C57BL/6J background and ten male wild-type (WT) mice of the same strain. Faeces were collected for bile acid analysis. Intestinal permeability was measured in an Ussing chamber upon euthanasia, using 4 kDa fluorescein isothiocyanate dextran, as per mille (‰, 1/1000) of translocated dextran. We analysed the liver expression of lipopolysaccharide-binding protein (LBP), as well as serum LBP (ELISA). Intestinal permeability was not affected by genetic obesity (jejunum: 0·234 (sem 0·04) ‰ for obese v. 0·225 (sem 0·03) ‰ for WT, P= 0·93; colon: 0·222 (sem 0·06) ‰ for obese v. 0·184 (sem 0·03) ‰ for WT, P= 0·86), nor was liver LBP expression (relative expression: 0·55 (sem 0·08) for obese v. 0·55 (sem 0·13) for WT, P= 0·70). Serum LBP was 2·5-fold higher in obese than in WT mice (P= 0·001). Obese mice had increased daily excretion of total bile acids, but their faecal bile acid hydrophobicity was unchanged. In conclusion, genetic obesity did not impair gut barrier function in mice on a regular chow diet, nor was faecal bile acid hydrophobicity affected.

scholarly journals The Role of Fatty Acids in Non-Alcoholic Fatty Liver Disease Progression: An Update

2021 ◽  
Vol 22 (13) ◽  
pp. 6900
Author(s):  
Aleksandra Hliwa ◽  
Bruno Ramos-Molina ◽  
Dariusz Laski ◽  
Adriana Mika ◽  
Tomasz Sledzinski
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Alcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Depth Analysis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.

Sign in / Sign up

Export Citation Format

Share Document