title: Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.
abstract: This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.
authors.affiliation: In Vitro Drug Safety and Biotechnology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: manuela.neuman@utoronto.ca.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.affiliation: Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.affiliation: Distilled Spirits Council, Washington, DC, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Zakhari
authors.affiliation: Department Internal Medicine, Kaplan Medical Centre and Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Stephen
authors.initials: S
authors.lastname: Malnick
authors.affiliation: Centre of Alcohol Research, University of Heidelberg, Heidelberg, Germany.
authors.forename: Helmut K
authors.initials: HK
authors.lastname: Seitz
authors.affiliation: Division of Gastroenterology, Sunnybrook Health Sciences Centre, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Cohen
authors.affiliation: Research Unit on Acetaldehyde and Cancer, University of Helsinki, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Salaspuro
authors.affiliation: Public Health Science Texas A&M University, College of Dentistry, Dallas University, TX, USA.
authors.forename: Andreea
authors.initials: A
authors.lastname: Voinea-Griffin
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Barasch
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Kirpich
authors.affiliation: Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomes
authors.affiliation: Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Schrum
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Donohue
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE, USA; Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.affiliation: In Vitro Drug Safety and Biotechnology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcus
authors.initials: M
authors.lastname: Cruz
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Family Medicine Clinic CAR, Bucharest, Romania.
authors.forename: Mihai
authors.initials: M
authors.lastname: Opris
mesh_terms: D000437:Alcoholism / Q000150:complications*; D003226:Congresses as Topic; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008019:Life Style; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D064307:Microbiota; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D019392:Cytochrome P-450 CYP2E1
keywords: Alcoholic hepatitis; Aldehyde dehydrogenase; CYP2E1; Colon carcinogenesis; Hepatocarcinogenesis; Immunohistochemistry; Laboratory markers; Mallory-Denk bodies; Mithocondrion; Nonalcoholic steatohepatitis; Oral health