Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

Manuela G. Neuman, Samuel W. French, Samir Zakhari, Stephen Malnick, Helmut K. Seitz, Lawrence B. Cohen, Mikko Salaspuro, Andreea Voinea-Griffin, Andrei Barasch, Irina A. Kirpich, Paul G Thomes, Laura W. Schrum, Terrence Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)162-180
Number of pages19
JournalExperimental and Molecular Pathology
Volume102
Issue number1
DOIs
StatePublished - Feb 1 2017

Fingerprint

Microbiota
Life Style
Liver
Alcohols
Liver Diseases
Fatty Liver
Alcoholic Hepatitis
Fibrosis
Ethanol
Translational Medical Research
Biomarkers
Alcoholism
Intestines
Metabolism
Tissue homeostasis
Th17 Cells
Cytochrome P-450 CYP2E1
Alcoholic Liver Diseases
Hyalin
Gastrointestinal Neoplasms

Keywords

  • Alcoholic hepatitis
  • Aldehyde dehydrogenase
  • CYP2E1
  • Colon carcinogenesis
  • Hepatocarcinogenesis
  • Immunohistochemistry
  • Laboratory markers
  • Mallory-Denk bodies
  • Mithocondrion
  • Nonalcoholic steatohepatitis
  • Oral health

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Neuman, M. G., French, S. W., Zakhari, S., Malnick, S., Seitz, H. K., Cohen, L. B., ... Opris, M. (2017). Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage. Experimental and Molecular Pathology, 102(1), 162-180. https://doi.org/10.1016/j.yexmp.2017.01.003

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage. / Neuman, Manuela G.; French, Samuel W.; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K.; Cohen, Lawrence B.; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A.; Thomes, Paul G; Schrum, Laura W.; Donohue, Terrence; Kharbanda, Kusum; Cruz, Marcus; Opris, Mihai.

In: Experimental and Molecular Pathology, Vol. 102, No. 1, 01.02.2017, p. 162-180.

Research output: Contribution to journalReview article

Neuman, MG, French, SW, Zakhari, S, Malnick, S, Seitz, HK, Cohen, LB, Salaspuro, M, Voinea-Griffin, A, Barasch, A, Kirpich, IA, Thomes, PG, Schrum, LW, Donohue, T, Kharbanda, K, Cruz, M & Opris, M 2017, 'Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage', Experimental and Molecular Pathology, vol. 102, no. 1, pp. 162-180. https://doi.org/10.1016/j.yexmp.2017.01.003
Neuman, Manuela G. ; French, Samuel W. ; Zakhari, Samir ; Malnick, Stephen ; Seitz, Helmut K. ; Cohen, Lawrence B. ; Salaspuro, Mikko ; Voinea-Griffin, Andreea ; Barasch, Andrei ; Kirpich, Irina A. ; Thomes, Paul G ; Schrum, Laura W. ; Donohue, Terrence ; Kharbanda, Kusum ; Cruz, Marcus ; Opris, Mihai. / Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage. In: Experimental and Molecular Pathology. 2017 ; Vol. 102, No. 1. pp. 162-180.
@article{0ca9bb3b59164a7eb3d57564271e95fe,
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.",
keywords = "Alcoholic hepatitis, Aldehyde dehydrogenase, CYP2E1, Colon carcinogenesis, Hepatocarcinogenesis, Immunohistochemistry, Laboratory markers, Mallory-Denk bodies, Mithocondrion, Nonalcoholic steatohepatitis, Oral health",
author = "Neuman, {Manuela G.} and French, {Samuel W.} and Samir Zakhari and Stephen Malnick and Seitz, {Helmut K.} and Cohen, {Lawrence B.} and Mikko Salaspuro and Andreea Voinea-Griffin and Andrei Barasch and Kirpich, {Irina A.} and Thomes, {Paul G} and Schrum, {Laura W.} and Terrence Donohue and Kusum Kharbanda and Marcus Cruz and Mihai Opris",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.yexmp.2017.01.003",
language = "English (US)",
volume = "102",
pages = "162--180",
journal = "Experimental and Molecular Pathology",
issn = "0014-4800",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

AU - Neuman, Manuela G.

AU - French, Samuel W.

AU - Zakhari, Samir

AU - Malnick, Stephen

AU - Seitz, Helmut K.

AU - Cohen, Lawrence B.

AU - Salaspuro, Mikko

AU - Voinea-Griffin, Andreea

AU - Barasch, Andrei

AU - Kirpich, Irina A.

AU - Thomes, Paul G

AU - Schrum, Laura W.

AU - Donohue, Terrence

AU - Kharbanda, Kusum

AU - Cruz, Marcus

AU - Opris, Mihai

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - Alcoholic hepatitis

KW - Aldehyde dehydrogenase

KW - CYP2E1

KW - Colon carcinogenesis

KW - Hepatocarcinogenesis

KW - Immunohistochemistry

KW - Laboratory markers

KW - Mallory-Denk bodies

KW - Mithocondrion

KW - Nonalcoholic steatohepatitis

KW - Oral health

UR - http://www.scopus.com/inward/record.url?scp=85010005238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010005238&partnerID=8YFLogxK

U2 - 10.1016/j.yexmp.2017.01.003

DO - 10.1016/j.yexmp.2017.01.003

M3 - Review article

C2 - 28077318

AN - SCOPUS:85010005238

VL - 102

SP - 162

EP - 180

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

SN - 0014-4800

IS - 1

ER -