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

Abstract

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.

Targeted Antimicrobial Agents as Potential Tools for Modulating the Gut Microbiome

“…The knowledge of narrow-spectrum antimicrobial agents has been greatly advanced in the past decade (see review: Fong et al, 2016 ; Maxson and Mitchell, 2016 ; Romani-Perez et al, 2017 ; George Kerry et al, 2018 ; Riglar and Silver, 2018 ; Alm and Lahiri, 2020 ; Altarac et al, 2021 ; Avis et al, 2021 ; Fuenzalida et al, 2021 ). Notably, some narrow-spectrum antimicrobial agents have entered clinical trials, mainly to combat bacteria associated with antibiotic resistance, such as Acinetobacter baumannii, S. aureus, P. aeruginosa, and E. coli (see review: Alm and Lahiri, 2020 ).…”

“…Besides the strategies reviewed in this article, probiotic and engineered bacteria have also been explored in modulating the gut microbiome. Effects of probiotics on the gut microbiome have been extensively reviewed ( George Kerry et al, 2018 ; Fuenzalida et al, 2021 ) and engineered bacteria is a complicated topic. When designing such engineered bacteria, multiple factors need to be considered including the selection of chassis bacteria, control circuits, secretion strategies, and payload proteins (see review: Mays and Nair, 2018 ; Aggarwal et al, 2020 ; Brennan, 2021 ; Lynch et al, 2022 ; Shen et al, 2022 ).…”

The immune response as a therapeutic target in non-alcoholic fatty liver disease

“…Recently, two not yet fully approved hypoglycemic drugs, glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT-2), showed effectiveness in reducing liver inflammation and fibrosis, mainly in a subgroup of diabetic patients in phase II and III trials ( 167 , 168 ). Moreover, different therapeutic approaches for liver diseases are focused on modulating the gut microbiota, including prebiotics and probiotics ( 169 ). The results of their evaluations support the benefit of this complementary strategy in NAFLD pharmacological therapy ( 170 , 171 ).…”

Role of Intestinal Microbes in Chronic Liver Diseases

“…Lactobacillus prevented AFLD by inhibiting oxidative stress, improving the function of the intestinal barrier, and reducing endotoxemia in the g intestine-liver axis [ 79 ]. The low number of Bacteroides and Firmicutes in the intestinal microbes of AFLD patients leads to dysbiosis of the intestinal ecology and overgrowth of pathogenic bacteria [ 80 ]. Lactobacillus could regulate the intestinal microbes of AFLD patients and normalize the intestinal microbes [ 81 ].…”