Gut Microbe Metabolites Can Modulate Heart Disease Risk, Study Reveals
Recent clinical research has indicated that phenylacetylglutamine (PAGln), a newly identified metabolite produced by gut microbes, may influence the risk of developing cardiovascular disease (CVD) and heart failure (HF).
A recent study published in Nature Communications investigates the mechanisms underlying the link between phenylacetylglutamine and negative cardiovascular effects.
Chronic non-communicable diseases account for nearly 75% of deaths worldwide. Cardiovascular diseases (CVDs), heart failure (HF), and related conditions represent a major portion of this mortality, highlighting the critical need to enhance current diagnostic and treatment methods.
As research progresses, the connection between diet, gut microbiota, and public health is becoming increasingly clear. Emerging evidence links gut microbial communities to various psychological and metabolic conditions, including obesity, diabetes, and Cardiovascular disease risk.
Several studies have suggested that phenylacetylglutamine (PAGln) may be associated with adverse cardiovascular events, with some research using phenylacetylglutamine levels in blood and feces as indicators to predict future Cardiovascular disease risk.
This study is the first to show that a metabolite from the gut microbiome can act as a natural modulator (NAM) of a host receptor, indicating a significant coevolution between the microbiome and its host.
The research found that phenylacetylglutamine affects cardiovascular tissue in a condition-dependent manner, acting as a partial activator of the β2AR receptor. Additionally, PAGln was recognized as an "ago-allosteric modulator," a unique type of modulator that works both as an agonist and an allosteric modulator depending on its interaction with other substances.
Overall, these findings suggest that phenylacetylglutamine could be a promising target for developing new treatments for cardiovascular diseases and that exploring the gut microbiome could offer new opportunities for tackling chronic illnesses.
Reference: Saha, P.P., Gogonea, V., Sweet, W. et al. (2024). Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors. Nature Communications 15; 6696. doi:10.1038/s41467-024-50855-3
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