Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

Purohit, Vishnudutt; Bode, J. Christian; Bode, Christiane; Brenner, David A.; Choudhry, Mashkoor A.; Hamilton, Frank A.; Kang, Y. James; Keshavarzian, Ali; Rao, Radhakrishna; Sartor, R. Balfour; Swanson, Christine; Turner, Jerrold R.

doi:10.1016/j.alcohol.2008.03.131

Cited by 277 publications

(250 citation statements)

References 93 publications

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“…In addition, alcohol metabolism by Gram-negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability by opening intestinal tight junctions. Increased intestinal permeability can lead to increased transfer of LPS from the intestine to portal and systemic circulation [28]. Furthermore, chronic alcohol consumption upregulates hepatic TLR4 and sensitizes it to LPS to enhance TNF-a production [29].…”

Section: Alcoholic Liver Diseasementioning

confidence: 99%

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

Soares¹,

et al. 2010

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Toll-like receptor 4 (TLR4) is a pattern recognition receptor that functions as lipopolysaccharide (LPS) sensor and whose activation results in the production of several pro-inflammatory, antiviral, and anti-bacterial cytokines. TLR4 is expressed in several cells of healthy liver. Despite the constant confrontation of hepatic TLR4 with gut-derived LPS, the normal liver does not show signs of inflammation due to its low expression of TLR4 and ability to modulate TLR4 signaling. Nevertheless, there is accumulating evidence that altered LPS/TLR4 signaling is a key player in the pathogenesis of many chronic liver diseases (CLD). In this review, we first describe TLR4 structure, ligands, and signaling. Later, we review liver expression of TLR4 and discuss the role of LPS/TLR4 signaling in the pathogenesis of CLD such as alcoholic liver disease, nonalcoholic fatty liver disease, chronic hepatitis C, chronic hepatitis B, primary sclerosing cholangitis, primary biliary cirrhosis, hepatic fibrosis, and hepatocarcinoma.

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Section: Alcoholic Liver Diseasementioning

confidence: 99%

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

Soares¹,

et al. 2010

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“…Evidence indicates that alcohol consumption causes enteric dysbiosis and bacterial overgrowth [139,140] that leads to a significant increase in gut permeability and consequently high levels of LPS in the portal circulation [141][142][143] . Acetaldehyde contributes to alter intestinal barrier function and to promote endotoxin translocation by disrupting tight and adherens junctions in human colonic mucosa [144] via increasing tyrosine phosphorylation of occludin and E-cadherin.…”

Section: Ethanol Oxidation and Activation Of Innate And Adaptive Immumentioning

confidence: 99%

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

Ceni

Mello

Galli

2014

WJG

413

339

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Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility. Key words: Alcohol metabolism; Acetaldehyde; Reactive oxygen species; Alcoholic liver disease; Protein adducts; Hepatic stellate cells; Liver fibrosis; CYP2E1Core tip: The goal of this article is to review the mechanisms of alcohol-mediated toxicity in parenchymal and non-parenchymal cells of the liver. Specifically, we highlight the effect of oxidative ethanol metabolites such as acetaldehyde and reactive oxygen species in the development of fat accumulation, fibrosis and deranged immune response.Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism.

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“…This study showed that Gln supplementation significantly increased LBP, which was in accordance with the study of Jafari et al (2006) where dairy cows were infused with 106 g/d and 212 g/d Gln. LBP can promote LPS to transfer to CD-14 to activate mononuclear macrophages and endothelial cells, which in turn activates Kupffer cells in liver to clear LPS via Toll-like receptors-4 (Purohit et al 2008). Furthermore, LBP can transfer LPS to serum lipoproteins, such as low-density lipoprotein (LDL) and highdensity lipoprotein (HDL), for clearing LPS from the bloodstream (Jafari et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…(2) Gln can prevent the reduction of transepithelial electrical resistance of intestinal epithelial cells caused by LPS, reduce the redistribution of occludin, zona occludens-1 (ZO-1), E-cadherin, and b-catenin from the intercellular junctions to the intracellular compartments, and decrease the acetaldehyde-induced dissociation of occludin, ZO-1, E-cadherin, and b-catenin from the actin cytoskeleton (Purohit et al 2008). (3) Gln can down-regulate the expression of intercellular adhesion molecule 1 in intestinal mucosa, thereby reduce its interaction with integrins including cluster of differentiation (CD)-11 and CD-18, so as to alleviate the activation and adhesion of neutrophils to intestinal endothelial cells, which helps to protect the intestinal mucosa (Gu et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary supplementation of glutamine and mannan oligosaccharides on plasma endotoxin and acute phase protein concentrations and nutrient digestibility in finishing steers

Jin

Dong

Lei

et al. 2013

Journal of Applied Animal Research

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This study was conducted to investigate the effects of dietary supplementation of glutamine (Gln) and mannan oligosaccharides (MOS) on plasma endotoxin and acute phase protein concentrations and nutrient apparent digestibility in finishing steers. Eighteen Simmental )Luxi crossbred finishing steers were randomly and evenly divided into three treatments: (1) the basal diet (control); (2) the basal diet ' 1% Gln; (3) the basal diet ' 0.2% MOS. The results showed: dietary supplementation of Gln decreased the plasma and fecal lipopolysaccharide (LPS) by 7.10% and 12.49%, respectively, but the differences did not attain statistical significance (P 0.05). The plasma concentrations of haptoglobin (Hp), serum amyloid A (SAA), and C-reactive protein (CRP) were not affected (P0.05), but the plasma concentration of LPS binding protein (LBP) was increased (PB0.01).

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Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

Abstract: This report is a summary of the symposium on Alcohol, Intestinal

Cited by 277 publications

References 93 publications

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

Effects of dietary supplementation of glutamine and mannan oligosaccharides on plasma endotoxin and acute phase protein concentrations and nutrient digestibility in finishing steers

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