title: 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 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.
authors.affiliation: Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room 2035, MSC 9304, Bethesda, MD 20892-9304, USA. vpurohit@nida.nih.gov
authors.forename: Vishnudutt
authors.initials: V
authors.lastname: Purohit
authors.forename: J Christian
authors.initials: JC
authors.lastname: Bode
authors.forename: Christiane
authors.initials: C
authors.lastname: Bode
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Frank
authors.initials: F
authors.lastname: Hamilton
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Rao
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Christine
authors.initials: C
authors.lastname: Swanson
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D018554:Avena / Q000378:metabolism; D018988:Bacterial Translocation / Q000187:drug effects*; D002056:Burns / Q000378:metabolism; D004731:Endotoxins / Q000097:blood / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005973:Glutamine / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010539:Permeability; D019936:Probiotics / Q000627:therapeutic use; D015032:Zinc / Q000378:metabolism
chemical_list: D004731:Endotoxins; D005973:Glutamine; D009569:Nitric Oxide; D000431:Ethanol; D066246:ErbB Receptors; D000079:Acetaldehyde; D015032:Zinc