Short-chain-fatty acid valerate reduces voluntary alcohol intake in male mice.

Background: Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. 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. Results: 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 acidshort-chain-fatty-acid with 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. Conclusion: Our findings suggest that the sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms.

Dietary Boswellia serrata Acid Alters the Gut Microbiome and Blood Metabolites in Experimental Models.

Boswellia serrata, commonly known as frankincense, has been used for centuries as a natural anti-inflammatory and anti-microbial remedy for many illnesses. However, the effect of the bioactive ingredient of it, 3-O-acetyl-11-keto-b-boswellic acid (AKBA), on both the gut microbiome and blood metabolites, is not known. In this study, we observe the effect of this isolated active ingredient orally on both male and female mice. Gut microbiota and blood metabolites were determined at the beginning and end of a 14-day consumption period. AKBA significantly decreased gut bacterial richness in male mice, and had no effect on female mice. Akkermansia muciniphila, associated with weight loss and anti-inflammation, was found to be significantly increased in both male and female mice, along with an increase in Bifidobacterium in female mice. Akkermansia muciniphila and Bifidobacterium were plated on media containing varying levels of AKBA (0%, 0.001%, 0.01%, and 0.1%). All concentrations of AKBA completely inhibited growth of Akkermansia muciniphila but had no effect on Bifidobacterium. Several blood metabolites differed with AKBA between both males and females. These results show the potential benefits of dietary Boswellia serrata on the modulation of gut microbiome composition, along with differences between sexes.