Journal article
Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice
Microbiome, v 12(1), p108
17 Jun 2024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied.BACKGROUNDDespite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied.Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome.RESULTSHere, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome.Our findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms. Video Abstract.CONCLUSIONOur findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms. Video Abstract.
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Details
- Title
- Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice
- Creators
- Suresh C Bokoliya - University of Connecticut Health CenterJordan Russell - University of Connecticut Health CenterYair Dorsett - University of Connecticut Health CenterHunter A Panier - University of Connecticut Health CenterVijender Singh - University of Connecticut Health CenterLauren Daddi - University of Connecticut Health CenterHanshu Yuan - University of Connecticut Health CenterLiv R Dedon - University of Connecticut Health CenterZhongmao Liu - University of ConnecticutYuqi Zhou - University of Connecticut Health CenterZefang MinJessica R Barson - Drexel UniversityJonathan Covault - University of Connecticut Health CenterJason A Bubier - Jackson LaboratoryYanjiao Zhou - University of Connecticut Health Center
- Publication Details
- Microbiome, v 12(1), p108
- Publisher
- Springer BMC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001268280600001
- Scopus ID
- 2-s2.0-85196524090
- Other Identifier
- 991021888115604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology