Gut Microbiota‐Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats
Journal
Journal of Extracellular Vesicles
ISSN
2001-3078
Date Issued
2025-03
Author(s)
Macarena Díaz‐Ubilla
Aliosha I. Figueroa‐Valdés
Hugo E. Tobar
María Elena Quintanilla
Eugenio Díaz
Paola Morales
Pablo Berríos‐Cárcamo
Daniela Santapau
Javiera Gallardo
Juan Ugalde
Carolina Rojas
Antonia Gonzalez‐Madrid
Yedy Israel
Francisca Alcayaga‐Miranda
Type
journal-article
Abstract
<jats:title>ABSTRACT</jats:title><jats:p>Growing preclinical and clinical evidence suggests a link between gut microbiota dysbiosis and problematic alcohol consumption. Extracellular vesicles (EVs) are key mediators involved in bacteria‐to‐host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota‐derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcohol‐drinking rat strain (UChB rats), either ethanol‐naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol‐rejecting male and female Wistar rats. Both types of UChB‐derived bEVs increased Wistar's voluntary alcohol consumption (three bottle choice test) up to 10‐fold (<jats:italic>p</jats:italic> < 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB‐derived bEVs operates through an inflammation‐independent mechanism. Furthermore, we demonstrate that the vagus nerve mediates the bEV‐induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota‐induced high alcohol intake in a vagus nerve‐dependent manner.</jats:p>
Subjects
alcohol drinking
;
animals
;
dysbiosis
;
ethanol
;
extracellular vesicles
;
female
;
gastrointestinal microbiome
;
male
;
rats
;
rats
;
wistar
;
vagus nerve
;
alcohol
;
alcohol consumption
;
animal experiment
;
animal model
;
animal tissue
;
article
;
controlled study
;
drinking behavior
;
exosome
;
female
;
hepatitis
;
high risk behavior
;
intestine flora
;
long term exposure
;
male
;
nervous system inflammation
;
nonhuman
;
rat
;
risk assessment
;
risk factor
;
species composition
;
vagotomy
;
vagus nerve
;
animal
;
drinking behavior
;
dysbiosis
;
metabolism
;
wistar rat
;
addictive behaviour
;
alcohol consumption
;
bacterial vesicles
;
bevs
;
gut microbiota
;
inflammation
;
microbiota-derived evs
;
vagus nerve