Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats

Only 30% of alcoholics develop liver disease (ALD) suggesting that addition al factors are needed. Endotoxin is one such factor, but its etiology is un clear. Since the gut is the main source of endotoxin, we sought to determin e whether an increase in intestinal permeability (leaky gut) is required fo r alcohol-induced endotoxemia and liver injury and whether the gut leakines s 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 p ermeability was then assessed by urinary excretion of lactulose and mannito l. Liver injury was evaluated histologically, biochemically (liver fat cont ent), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these cha nges. We conclude that chronic gavage of alcohol in rats is a simple experi mental model that mimics key aspects of ALD, including endotoxemia and live r injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxe mia and ameliorated liver damage in rat, our results suggest that alcohol-i nduced gut leakiness 1) may cause alcohol-induced endotoxemia and liver inj ury and 2) may be the critical cofactor in the 30% of alcoholics who develo p 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.