Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats
Abstract Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression o...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-80228-1 |
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| author | María Elena Quintanilla Daniela Santapau Eugenio Diaz Ignacio Valenzuela Martinez Nicolas Medina Glauben Landskron Antonia Dominguez Paola Morales David Ramírez Marcela Hermoso Belén Olivares Pablo Berríos-Cárcamo Marcelo Ezquer Mario Herrera-Marschitz Yedy Israel Fernando Ezquer |
| author_facet | María Elena Quintanilla Daniela Santapau Eugenio Diaz Ignacio Valenzuela Martinez Nicolas Medina Glauben Landskron Antonia Dominguez Paola Morales David Ramírez Marcela Hermoso Belén Olivares Pablo Berríos-Cárcamo Marcelo Ezquer Mario Herrera-Marschitz Yedy Israel Fernando Ezquer |
| author_sort | María Elena Quintanilla |
| collection | DOAJ |
| description | Abstract Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression of alcohol use disorder. Among the different protective molecules that could mediate this communication, short chain fatty acids (SCFAs) have emerged as attractive candidates, since these gut microbiota-derived molecules have multi-target effects that could normalize several of the functional and structural parameters altered by chronic alcohol abuse. The present study, conducted in male alcohol-preferring UChB rats, shows that the initiation of voluntary ethanol intake was inhibited in 85% by the intragastric administration of a combination of SCFAs (acetate, propionate and butyrate) given before ethanol exposure, while SCFAs administration after two months of ethanol intake induced a 90% reduction in its consumption. These SCFAs therapeutic effects were associated with (1) a significant reduction of ethanol-induced intestinal inflammation and damage; (2) reduction of plasma lipopolysaccharide levels and hepatic inflammation; (3) reduction of ethanol-induced astrocyte and microglia activation; and (4) attenuation of the ethanol-induced gene expression changes within the nucleus accumbens. Finally, we determined that among the different SCFAs evaluated, butyrate was the most potent, reducing chronic ethanol intake in a dose–response manner. These findings support a key role of SCFAs, and especially butyrate, in regulating AUD, providing a simple, inexpensive, and safe approach as a preventive and intervention-based strategy to address this devastating disease. |
| format | Article |
| id | doaj-art-f6ed752d118c41c4a83889d462d6c5e7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f6ed752d118c41c4a83889d462d6c5e72024-12-01T12:20:21ZengNature PortfolioScientific Reports2045-23222024-11-0114111610.1038/s41598-024-80228-1Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in ratsMaría Elena Quintanilla0Daniela Santapau1Eugenio Diaz2Ignacio Valenzuela Martinez3Nicolas Medina4Glauben Landskron5Antonia Dominguez6Paola Morales7David Ramírez8Marcela Hermoso9Belén Olivares10Pablo Berríos-Cárcamo11Marcelo Ezquer12Mario Herrera-Marschitz13Yedy Israel14Fernando Ezquer15Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de ChileCenter for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del DesarrolloDepartment of Neuroscience, Faculty of Medicine, Universidad de ChileDepartamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de ConcepciónDepartamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de ConcepciónCenter for Biomedical Research, CIBMED, Faculty of Medicine, Universidad Finis TerraeCenter for Biomedical Research, CIBMED, Faculty of Medicine, Universidad Finis TerraeMolecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de ChileDepartamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de ConcepciónDepartment of Gastroenterology and Hepatology, University Medical CenterCenter for Medical Chemistry, Faculty of Medicine Clínica Alemana-Universidad del DesarrolloCenter for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del DesarrolloCenter for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del DesarrolloDepartment of Neuroscience, Faculty of Medicine, Universidad de ChileMolecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de ChileCenter for Regenerative Medicine, Faculty of Medicine Clínica Alemana-Universidad del DesarrolloAbstract Alcohol use disorder (AUD) represents a public health crisis with few FDA-approved medications for its treatment. Growing evidence supports the key role of the bidirectional communication between the gut microbiota and the central nervous system (CNS) during the initiation and progression of alcohol use disorder. Among the different protective molecules that could mediate this communication, short chain fatty acids (SCFAs) have emerged as attractive candidates, since these gut microbiota-derived molecules have multi-target effects that could normalize several of the functional and structural parameters altered by chronic alcohol abuse. The present study, conducted in male alcohol-preferring UChB rats, shows that the initiation of voluntary ethanol intake was inhibited in 85% by the intragastric administration of a combination of SCFAs (acetate, propionate and butyrate) given before ethanol exposure, while SCFAs administration after two months of ethanol intake induced a 90% reduction in its consumption. These SCFAs therapeutic effects were associated with (1) a significant reduction of ethanol-induced intestinal inflammation and damage; (2) reduction of plasma lipopolysaccharide levels and hepatic inflammation; (3) reduction of ethanol-induced astrocyte and microglia activation; and (4) attenuation of the ethanol-induced gene expression changes within the nucleus accumbens. Finally, we determined that among the different SCFAs evaluated, butyrate was the most potent, reducing chronic ethanol intake in a dose–response manner. These findings support a key role of SCFAs, and especially butyrate, in regulating AUD, providing a simple, inexpensive, and safe approach as a preventive and intervention-based strategy to address this devastating disease.https://doi.org/10.1038/s41598-024-80228-1Alcohol abuseGut microbiota-brain axisSCFAsButyrateAlcohol use disorder treatment |
| spellingShingle | María Elena Quintanilla Daniela Santapau Eugenio Diaz Ignacio Valenzuela Martinez Nicolas Medina Glauben Landskron Antonia Dominguez Paola Morales David Ramírez Marcela Hermoso Belén Olivares Pablo Berríos-Cárcamo Marcelo Ezquer Mario Herrera-Marschitz Yedy Israel Fernando Ezquer Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats Scientific Reports Alcohol abuse Gut microbiota-brain axis SCFAs Butyrate Alcohol use disorder treatment |
| title | Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| title_full | Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| title_fullStr | Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| title_full_unstemmed | Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| title_short | Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| title_sort | intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats |
| topic | Alcohol abuse Gut microbiota-brain axis SCFAs Butyrate Alcohol use disorder treatment |
| url | https://doi.org/10.1038/s41598-024-80228-1 |
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