Vol. 299, Issue 2, 442-448, November 2001

Preventing Gut Leakiness by Oats Supplementation Ameliorates Alcohol-Induced Liver Damage in Rats

Ali Keshavarzian , Sandeep Choudhary, Earle W. Holmes, Sherri Yong, Ali Banan , Shriram Jakate and Jeremy Z. Fields

Section of Gastroenterology and Nutrition, Division of Digestive Diseases, Departments of Internal Medicine (A.K., S.C., A.B., S.J., J.Z.F.), Pharmacology (A.K., A.B.), Physiology and Molecular Biophysics (A.K.), and Pathology (S.J.), Rush Presbyterian St. Lukes Medical Center, Chicago, Illinois; and Department of Pathology (E.W.H., S.Y.), Loyola University Medical Center, Maywood, Illinois

Only 30% of alcoholics develop liver disease (ALD) suggesting that additional factors are needed. Endotoxin is one such factor, but its etiology is unclear. Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes. We conclude that chronic gavage of alcohol in rats is a simple experimental model that mimics key aspects of ALD, including endotoxemia and liver injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxemia and ameliorated liver damage in rat, our results suggest that alcohol-induced gut leakiness 1) may cause alcohol-induced endotoxemia and liver injury and 2) may be the critical cofactor in the 30% of alcoholics who develop ALD. Further studies are needed to determine whether ALD in humans can be prevented by preventing alcohol-induced gut leakiness, studies that should lead to the development of useful therapeutic agents for the prevention of ALD.