Alcohol and the Intestine

Patel, Sheena; Behara, Rama; Swanson, Garth; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

doi:10.3390/biom5042573

Cited by 76 publications

(69 citation statements)

References 117 publications

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“…Endotoxemia is closely related to the pathogenesis of ALD and stimulates the production of proinflammatory cytokines [36]. This study suggests that alcohol feeding increases serum endotoxin level.…”

Section: Discussionmentioning

confidence: 77%

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Xue¹,

Liu²,

Lyu³

et al. 2017

PLoS ONE

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BackgroundThis study investigated the protective effect of aplysin on the liver and its influence on inflammation and the gut microbiota in rats with ethanol-induced liver injury.MethodsMale Sprague-Dawley rats were randomly assigned to an alcohol-containing liquid diet, control liquid diet or treatment with aplysin for 8 weeks. Hepatic and intestinal histopathological analysis was performed, and cytokine levels and the intestinal mucosal barrier were assessed. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and 16S rDNA high-throughput sequencing were performed to provide an overview of the gut microbiota composition.ResultsChronic alcohol exposure caused liver damage in rats. Serum aspartate aminotransferase (AST), aminotransferase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) activities in liver tissue were higher than in the control group. Alcohol administration elevated the levels of serum transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) and reduced interleukin-10 (IL-10) levels compared with those of control rats. In addition, the levels of plasma endotoxin, diamine oxidase (DAO), and fatty acid-binding protein 2 (FABP2) in the alcohol group were higher than in the control group. The results of ERIC-PCR indicated that aplysin treatment shifted the overall structure of the ethanol-disrupted gut microbiota toward that of the control group. One hundred twenty to 190 genera of bacteria were detected by high throughput sequencing. Alcohol-induced changes in the gut microbial composition were detected at the genus level. These alcohol-induced effects could be reversed with aplysin treatment.ConclusionsThese results suggest that aplysin exerts a protective effect on ethanol-induced hepatic injury in rats by normalizing fecal microbiota composition and repairing intestinal barrier function.

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Section: Discussionmentioning

confidence: 77%

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Xue¹,

Liu²,

Lyu³

et al. 2017

PLoS ONE

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“…Since blood from the intestines drains into the venous portal system, it is the liver that first encounters elevated levels of lipopolysaccharide (LPS) and other gut‐derived pathogen associated molecular patterns (PAMPs) (Patel et al. ; Szabo ). A growing body of evidence suggests that the resulting liver inflammatory response, primarily driven via LPS‐Toll‐Like Receptor‐4 (TLR‐4) interactions on liver‐resident Kupffer cells, promotes ALD pathogenesis (Wang et al.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of junctional adhesion molecule‐A contributes to ethanol‐induced barrier disruption in intestinal epithelial cell monolayers

et al. 2017

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Alcohol consumption promotes loss of intestinal barrier function. However, mechanisms by which ethanol affects the tight junction (TJ), the cellular structure responsible for maintaining the gut epithelial barrier, are not well understood. Three classes of transmembrane proteins comprise TJs: occludin, claudins, and junctional adhesion molecules (JAMs). It has recently been postulated that JAM‐A (F11R), the most abundant JAM expressed in intestinal epithelium, regulates “leak” pathway flux, a paracellular route for the nonselective permeation of large solutes. Since transluminal flux of many gut‐derived antigens occurs through this pathway, we investigated the role of JAM‐A in ethanol‐induced disruption of the intestinal epithelial barrier. Using Caco‐2 and SK‐CO15 monolayers, we found that ethanol induced a dose‐ and time‐dependent decrease in JAM‐A protein expression to about 70% of baseline levels. Alcohol also reduced Ras‐related protein 2 (Rap2) activity, and enhanced myosin light chain kinase (MLCK) activity, changes consistent with impaired JAM‐A signaling. Stable overexpression and shRNA‐mediated knockdown of JAM‐A were employed to investigate the role of JAM‐A in paracellular‐mediated flux following alcohol exposure. The paracellular flux of 40‐kDa fluorescein isothiocynate (FITC)‐dextran following ethanol treatment was decreased by the overexpression of JAM‐A; conversely, flux was enhanced by JAM‐A knockdown. Thus, we conclude that ethanol‐mediated control of JAM‐A expression and function contributes to mechanisms by which this chemical induces intestinal epithelial leakiness.

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“…Alcohol consumption causes intestinal inflammation, which is associated with accelerated polyposis [10,11]. We have shown that intestinal inflammation from alcohol is exacerbated by the disruption of circadian rhythms from shifting light:dark (LD) cycles [12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

Bishehsari

Saadalla

Khazaie

et al. 2016

IJMS

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Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

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Alcohol and the Intestine

Cited by 76 publications

References 117 publications

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Dysregulation of junctional adhesion molecule‐A contributes to ethanol‐induced barrier disruption in intestinal epithelial cell monolayers

Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

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