Alcohol and the Intestine.
Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches.
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Sheena_K_Patel@rush.edu.
Sheena
S
Patel
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Ramakrishna_V_Behara@rush.edu.
Rama
R
Behara
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Garth_Swanson@rush.edu.
Garth R
GR
Swanson
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Christopher_Forsyth@rush.edu.|Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA. Christopher_Forsyth@rush.edu.
Christopher B
CB
Forsyth
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Robin_Voigt@rush.edu.
Robin M
RM
Voigt
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA. Ali_keshavarzian@rush.edu.|Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA. Ali_keshavarzian@rush.edu.|Department of Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, IL 60612, USA. Ali_keshavarzian@rush.edu.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht PO Box 80125, The Netherlands. Ali_keshavarzian@rush.edu.
Ali
A
Keshavarzian
D000818:Animals; D064806:Dysbiosis / Q000209:etiology; D019446:Endotoxemia / Q000209:etiology; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*
D000431:Ethanol
alcohol; dysbiosis; endotoxemia; gut leakiness