Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Aug;42(5):349-61.
doi: 10.1016/j.alcohol.2008.03.131. Epub 2008 May 27.

Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences: Summary of a Symposium

Affiliations
Free PMC article

Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences: Summary of a Symposium

Vishnudutt Purohit et al. Alcohol. .
Free PMC article

Abstract

This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram-negative bacteria in the intestine, which may result in accumulation of endotoxin. 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 to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan, which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram-negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, l-glutamine, oats supplementation, or zinc, thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram-negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries.

Figures

Figure 1
Figure 1. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and organ injury: a summary
Alcohol exposure can promote the growth of Gram negative bacteria in the intestine which may result in accumulation of endotoxin. 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 to endotoxin. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin. Increased intestinal permeability to endotoxin leads to increased transfer of endotoxin from the intestine to the portal vein which carries endotoxin to the liver where it binds to Kupffer cells and initiates a cascade of events leading to tumor necrosis factor-α (TNF-α) production and liver injury. Endotoxin that escapes to general circulation may induce injury to other organs. A part of TNF- α produced in the liver may reach to intestine via bile duct or general circulation and further increase intestinal permeability to endotoxin.
Figure 2
Figure 2. Role of acetaldehyde in increasing intestinal permeability to endotoxin: a proposed mechanism
Acetaldehyde may increase intestinal permeability to endotoxin by decreasing the activity of protein tyrosine phosphatase in the intestinal epithelial paracellular space. This results in the increased tyrosine phosphorylation of tight junction proteins (occludin and ZO-1) and adherens junction proteins (E-cadherin and β-catenin). Increased phosphorylation of these proteins leads to their redistribution from intercellular junctions to intracellular compartments and that probably results in increased intestinal permeability to endotoxin.
Figure 3
Figure 3. Role of nitric oxide in increasing intestinal permeability to endotoxin: a proposed mechanism
Alcohol may also increase intestinal permeability by increasing the production of nitric oxide, via up-regulating inducible nitric oxide synthase (iNOS) activity, and superoxide. These radicals can react with each other to form peroxynitrite which in turn can react with tubulin leading to damage to microtubule cytoskeleton, disruption of barrier function, and increased intestinal permeability.
Figure 4
Figure 4. Role of TNF-α in intestinal barrier function
In intestinal inflammatory diseases, TNF-α may play an important role in impairing intestinal barrier function by upregulating the activity of myosin light-chain kinase (MLCK) and associated increased phosphorylation of myosin light-chain (MLC).
Figure 5
Figure 5. Strategies for attenuating plasma endotoxin levels in alcoholic liver diseases
Plasma endotoxin levels may be attenuated by reducing the number of Gram negative bacteria in the intestine or preserving intestinal permeability to endotoxin. The number of Gram negative bacteria can be reduced by feeding probiotics such as Lactobacillus GG or Bifidobacteria. This can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor (EGF), L-glutamine, oat supplementation, or zinc which is expected to prevent the transfer of endotoxin to the general circulation.

Similar articles

See all similar articles

Cited by 116 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback