Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches

The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur in AUD even before any other systemic signs or symptoms manifes...

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Main Authors: Emilio Merlo Pich, Ioannis Tarnanas, Patrizia Brigidi, Ginetta Collo
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Neurobiology of Stress
Online Access:http://www.sciencedirect.com/science/article/pii/S2352289525000074
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author Emilio Merlo Pich
Ioannis Tarnanas
Patrizia Brigidi
Ginetta Collo
author_facet Emilio Merlo Pich
Ioannis Tarnanas
Patrizia Brigidi
Ginetta Collo
author_sort Emilio Merlo Pich
collection DOAJ
description The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur in AUD even before any other systemic signs or symptoms manifest. Prolonged and inappropriate alcohol consumption, by affecting the gut microbiota and gut mucosa permeability, is thought to contribute to the development of behavioral and cognitive impairments, leading to Alcohol-Related Liver Disorders and potentially progressing into alcoholic cirrhosis, which is often associated with severe cognitive impairment related to neurodegeneration, such as hepatic encephalopathy and alcoholic dementia.The critical role of the gut microbiota is further supported by the efficacy of FDA-approved treatments for hepatic encephalopathy in alcoholic cirrhosis (i.e., lactulose and rifaximin). To stimulate new research, we hypothesize that interactions between a maladaptive stress response and a constitutional predisposition to neurodegeneration underlie the progression of AUD to conditions of Alcohol-Related Clinical Concerns with severe cognitive impairment, which represent a significant and costly burden to society. Early identification of AUD individuals at risk for developing these conditions could help to prioritize integrated therapeutic interventions targeting different substrates of the Gut Microbiome-Liver-Brain axis. Specifically, addiction medications, microbiome modulators, stress-reducing interventions, and, possibly soon, novel agents that reduce hepatic steatosis/fibrosis will be discussed in the context of digitally supported integrated therapeutic approaches. The explicit goal of this AUD treatment performed on the early stage of the disorder would be to reduce the transition from AUD to those conditions of Alcohol-Related Common Clinical Concerns associated with severe cognitive impairment, a strategy recommended for most neurological neurodegenerative disorders.
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spelling doaj-art-91501aa3e99841d59e6a7fa6542c2aaf2025-08-20T02:51:53ZengElsevierNeurobiology of Stress2352-28952025-03-013510071310.1016/j.ynstr.2025.100713Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approachesEmilio Merlo Pich0Ioannis Tarnanas1Patrizia Brigidi2Ginetta Collo3Gelf Health, Milano, Italy; Corresponding author. Gelf Health, via Romagnosi 4, Milano, Italy.Trinity College Dublin, Global Brain Health Institute, Dublin, Ireland; Altoida Inc., Washington DC, USAHuman Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, ItalyHuman Neuropharmacology Unit, Department of Molecular & Translational Medicine, University of Brescia, ItalyThe Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur in AUD even before any other systemic signs or symptoms manifest. Prolonged and inappropriate alcohol consumption, by affecting the gut microbiota and gut mucosa permeability, is thought to contribute to the development of behavioral and cognitive impairments, leading to Alcohol-Related Liver Disorders and potentially progressing into alcoholic cirrhosis, which is often associated with severe cognitive impairment related to neurodegeneration, such as hepatic encephalopathy and alcoholic dementia.The critical role of the gut microbiota is further supported by the efficacy of FDA-approved treatments for hepatic encephalopathy in alcoholic cirrhosis (i.e., lactulose and rifaximin). To stimulate new research, we hypothesize that interactions between a maladaptive stress response and a constitutional predisposition to neurodegeneration underlie the progression of AUD to conditions of Alcohol-Related Clinical Concerns with severe cognitive impairment, which represent a significant and costly burden to society. Early identification of AUD individuals at risk for developing these conditions could help to prioritize integrated therapeutic interventions targeting different substrates of the Gut Microbiome-Liver-Brain axis. Specifically, addiction medications, microbiome modulators, stress-reducing interventions, and, possibly soon, novel agents that reduce hepatic steatosis/fibrosis will be discussed in the context of digitally supported integrated therapeutic approaches. The explicit goal of this AUD treatment performed on the early stage of the disorder would be to reduce the transition from AUD to those conditions of Alcohol-Related Common Clinical Concerns associated with severe cognitive impairment, a strategy recommended for most neurological neurodegenerative disorders.http://www.sciencedirect.com/science/article/pii/S2352289525000074
spellingShingle Emilio Merlo Pich
Ioannis Tarnanas
Patrizia Brigidi
Ginetta Collo
Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
Neurobiology of Stress
title Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
title_full Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
title_fullStr Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
title_full_unstemmed Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
title_short Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches
title_sort gut microbiome liver brain axis in alcohol use disorder the role of gut dysbiosis and stress in alcohol related cognitive impairment progression possible therapeutic approaches
url http://www.sciencedirect.com/science/article/pii/S2352289525000074
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