Gut Microbiota‐Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats

ABSTRACT 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 u...

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Main Authors: Macarena Díaz‐Ubilla, Aliosha I. Figueroa‐Valdés, Hugo E. Tobar, María Elena Quintanilla, Eugenio Díaz, Paola Morales, Pablo Berríos‐Cárcamo, Daniela Santapau, Javiera Gallardo, Cristian deGregorio, Juan Ugalde, Carolina Rojas, Antonia Gonzalez‐Madrid, Marcelo Ezquer, Yedy Israel, Francisca Alcayaga‐Miranda, Fernando Ezquer
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Journal of Extracellular Vesicles
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Online Access:https://doi.org/10.1002/jev2.70059
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Summary:ABSTRACT 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 (p < 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.
ISSN:2001-3078