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 regress...

Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease

“…Indeed, ethanol has been shown to have many effects on the liver. It reaches the liver via the portal vein, induces triglyceride accumulation and hepatic oxidative stress in the liver, and also increases gut permeability . Zhu et al demonstrated that patients with NASH exhibit significantly elevated blood ethanol levels compared to those without NASH .…”

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk

“…Through the portal vein that connects the liver to the gastrointestinal tract, the liver is exposed to the influence of the gut microbiome. Perturbations of the gut microbiome, coupled with disturbances in gut barrier function, have been associated with common liver disorders, such as non-alcoholic fatty liver disease [138][139][140], non-alcoholic steatohepatitis [139,[141][142][143][144][145][146][147][148][149][150][151][152], alcoholic liver disease [139,140,142,145,147,148,150,151,[153][154][155][156][157][158][159][160][161][162][163][164], and liver cirrhosis [165][166][167][168][169][170]. Thus, the microbiome serves as a modulator of liver rhythmic functions.…”

Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis

“…(32,33) Additionally, ethanol reaches the liver through the portal vein, inducing triglyceride accumulation and hepatic oxidative stress, and increasing gut permeability. (34) Previous epidemiological studies have suggested a synergistic effect of alcohol and obesity on liver disease morbidity and mortality. (18,19) In our study, there were significant interactions between obesity and alcohol intake categories for incident HS, and between obesity and alcohol intake categories for incident HS plus an intermediate/high probability of advanced fibrosis.…”