Gut-Liver-Brain Axis and Alcohol Use Disorder: Treatment Potential of Fecal Microbiota Transplantation

Abstract

PURPOSE Chronic alcohol use is a major cause of liver damage and death. In the United States, multiple factors have led to low utilization of pharmacotherapy for alcohol use disorder (AUD), including lack of provider knowledge and comfort in prescribing medications for AUD. Alcohol consumption has direct effects on the gut microbiota, altering the diversity of bacteria and leading to bacterial overgrowth. Growing evidence suggests that alcohol’s effects on the gut microbiome may contribute to increased alcohol consumption and progression of alcohol-associated liver disease (ALD). This article reviews human and preclinical studies investigating the role of fecal microbiota transplantation (FMT) in ameliorating alcohol-associated alterations to the liver, gut, and brain resulting in altered behavior; it also discusses the therapeutic potential of FMT. SEARCH METHODS For this narrative review, a literature search was conducted in September 2022 of PubMed, Web of Science Core Collection, and Google Scholar to identify studies published between January 2012 and September 2022. Search terms used included “fecal microbiota transplantation” and “alcohol.” SEARCH RESULTS Most results of the literature search were review articles or articles on nonalcoholic fatty liver disease; these were excluded. Of the remaining empirical manuscripts, very few described clinical or preclinical studies that were directly investigating the effects of FMT on alcohol drinking or related behaviors. Ultimately, 16 studies were included in the review. DISCUSSION AND CONCLUSIONS The literature search identified only a few studies that were directly investigating the effect of FMT on ALD or alcohol drinking and related behaviors. Largely proof-of-concept studies, these findings demonstrate that alcohol can alter the gut microbiome and that the microbiome can be transferred between humans and rodents to alter affective behaviors frequently associated with increased alcohol use. Other studies have shown promise of FMT or other probiotic supplementation in alleviating some of the symptoms associated with ALD and drinking. These results show that the implementation of FMT as a therapeutic approach is still in the investigatory stages.

Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity

“…However, this deficiency in high-fat diet-induced DA release can be corrected by the dietary satiety mediator oleoylethanolamine ( Ren et al, 2010 ; de Araujo et al, 2012 ; Ferreira et al, 2012 ). Similarly, it is possible that therapies targeting the gut microbiome, such as probiotics and fecal microbiota transplant, could be viable approaches to treat substance use disorders ( Fuenzalida et al, 2021 ; Pizarro et al, 2021 ; Wolstenholme et al, 2024 ).…”

Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application

“…In particular, chronic inflammatory conditions may lead to alterations in several inflammatory mediators that can activate the nuclear factor kappa B (NF-kB) signaling pathway, leading to neuronal damage/apoptosis in glial and/or neuronal cells [73]. It is important to note that not all patients with alcohol dependency have dysbiosis and/or increased gut epithelial disruption [74]. However, several effects of alcohol on the gut microbiome might contribute to increased alcohol consumption.…”

“…However, several effects of alcohol on the gut microbiome might contribute to increased alcohol consumption. Therefore, the use of probiotics, prebiotics, or FMT may deserve further investigation as therapeutic tactics for alcohol dependency [74]. At present, however, the application of FMT as a therapeutic approach is still in the investigatory stages [74].…”

“…Therefore, the use of probiotics, prebiotics, or FMT may deserve further investigation as therapeutic tactics for alcohol dependency [74]. At present, however, the application of FMT as a therapeutic approach is still in the investigatory stages [74]. Stool donor-to-recipient disease transfer is a great concern of FMT.…”