AI Article Synopsis
- The study investigates how gut microbial metabolites (GMM), specifically phenylacetylglutamine (PAGln), are linked to cardiovascular diseases (CVD) in people with alcohol use disorder.
- In experiments with mice, researchers found that chronic alcohol consumption led to changes in gut microbes and increased PAGln levels, which were associated with cardiovascular issues.
- PAGln was shown to cause heart and blood vessel problems independent of alcohol, indicating that it plays a significant role in the development of CVD related to alcohol consumption.
Article Abstract
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.
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| http://dx.doi.org/10.1038/s41467-024-55084-2 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685538 | PMC |
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