title: Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.
abstract: Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, "probiotic"Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague-Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5 x 10(7) live L. rhamnosus Gorbach-Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol+LGG (ALC+LGG)-fed rats had significantly (P< or =.05) less severe ASH than ALC+V-fed rats. L. rhamnosus Gorbach-Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach-Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases and Nutrition, and Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, IL 60612, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Forsyth
authors.forename: Ashkan
authors.initials: A
authors.lastname: Farhadi
authors.forename: Shriram M
authors.initials: SM
authors.lastname: Jakate
authors.forename: Yueming
authors.initials: Y
authors.lastname: Tang
authors.forename: Maliha
authors.initials: M
authors.lastname: Shaikh
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000517:prevention & control; D041981:Gastrointestinal Tract / Q000382:microbiology; D007408:Intestinal Absorption / Q000187:drug effects; D052201:Lacticaseibacillus rhamnosus; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley