Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut–brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

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Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.729950 ◽

2021 ◽

Vol 12 ◽

Author(s):

Catalina Fuenzalida ◽

María Soledad Dufeu ◽

Jaime Poniachik ◽

Juan Pablo Roblero ◽

Lucía Valenzuela-Pérez ◽

...

Keyword(s):

Liver Disease ◽

Alcohol Consumption ◽

Alcohol Use ◽

Gut Microbiota ◽

Liver Damage ◽

Alcoholic Liver Disease ◽

Alcohol Use Disorder ◽

Autism Spectrum ◽

Microbial Composition ◽

The Impact

Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer’s, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.

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Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

Liver International ◽

10.1111/liv.14383 ◽

2020 ◽

Vol 40 (4) ◽

pp. 878-888 ◽

Cited By ~ 7

Author(s):

Giovanni Addolorato ◽

Francesca R. Ponziani ◽

Tommaso Dionisi ◽

Carolina Mosoni ◽

Gabriele A. Vassallo ◽

...

Keyword(s):

Liver Disease ◽

Alcohol Use ◽

Gut Microbiota ◽

Alcohol Use Disorder

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Approaching Alcohol Use Disorder After Liver Transplantation for Acute Alcoholic Hepatitis

Clinics in Liver Disease ◽

10.1016/j.cld.2021.03.008 ◽

2021 ◽

Author(s):

Peng-Sheng Ting ◽

Ahmet Gurakar ◽

Jason Wheatley ◽

Geetanjali Chander ◽

Andrew M. Cameron ◽

...

Keyword(s):

Liver Transplantation ◽

Alcohol Use ◽

Alcoholic Hepatitis ◽

Alcohol Use Disorder ◽

Acute Alcoholic Hepatitis

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Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2021.05.066 ◽

2021 ◽

Author(s):

Lu-Lu Gao ◽

Jia-Min Ma ◽

Yan-Na Fan ◽

Yan-Nan Zhang ◽

Rui Ge ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Intestinal Barrier ◽

Hepatic Inflammation ◽

Lycium Barbarum ◽

Nonalcoholic Fatty Liver ◽

Lycium Barbarum Polysaccharide

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Serum HMGB1 Associates with Liver Disease and Predicts Readmission and Mortality in Patients with Alcohol Use Disorder

Alcohol ◽

10.1016/j.alcohol.2021.05.003 ◽

2021 ◽

Author(s):

Augustin G.L. Vannier ◽

Ben Wardwell ◽

Vladislav Fomin ◽

Amanda Pebenito ◽

Nicholas Wolczynski ◽

...

Keyword(s):

Liver Disease ◽

Alcohol Use ◽

Alcohol Use Disorder

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Study of brainstem auditory evoked response and biochemical markers in patients of alcohol use disorder

Indian Journal of Physiology and Pharmacology ◽

10.25259/ijpp_2018_oa105_m ◽

2021 ◽

Vol 65 ◽

pp. 193-200

Author(s):

Mudassir Anis Siddiqui ◽

Divya Srivastava ◽

Sandeep Choudhary

Keyword(s):

Alcohol Use ◽

Biochemical Parameters ◽

Alcoholic Hepatitis ◽

Alcohol Use Disorder ◽

Liver Enzymes ◽

Evoked Response ◽

Transmission Time ◽

Control Group ◽

Auditory Evoked Response ◽

Brainstem Auditory Evoked Response

Objectives: Data available on brainstem auditory evoked response (BAER) and its correlation with biochemical parameters in patients of alcohol use disorder (AUD) in Indian population is scanty. Therefore, this study was undertaken to focus on the effects of AUD on BAER and liver enzymes. Materials and Methods: This case-control study included 40 males in the study group who had AUD and 40 healthy males in the control group in the age group of 20–60 years. The BAER was performed using octopus NCS/ EMG/EP (Clarity) machine. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and serum bilirubin were estimated in all the subjects. Results: We observed a highly significant increase in the absolute latencies of waves III and V and interpeak latencies (IPL) I-III and I-V of BAER in the patients of AUD in this study. Significant increase in the liver enzymes and especially AST/ALT ratio of patients of AUD was seen which indicated towards subclinical alcoholic hepatitis. The latencies of waves of EPs (waves III, V, IPL I-III and IPL I-V) were positively correlated with the biochemical parameters and duration of AUD. Conclusion: Our findings indicated that AUD lead to the increase in brainstem transmission time and also lead to subclinical alcoholic hepatitis which is reflected by the increase in the liver enzymes. We concluded that chronic alcohol consumption affected the auditory pathways and delayed the auditory transmission time which was suggestive of possible demyelination of auditory tracts.

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Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder

Frontiers in Physiology ◽

10.3389/fphys.2021.699253 ◽

2021 ◽

Vol 12 ◽

Author(s):

Phillipp Hartmann ◽

Sonja Lang ◽

Suling Zeng ◽

Yi Duan ◽

Xinlian Zhang ◽

...

Keyword(s):

Liver Disease ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

Serum Levels ◽

Amplicon Sequencing ◽

Dynamic Changes ◽

Alcohol Abstinence ◽

Liver Health ◽

Fungal Microbiome ◽

Progressive Liver Disease

BackgroundAlcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein.MethodsWe studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples.ResultsPatients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease.ConclusionIn conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.

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