Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota

Area of Science:

• Cardiovascular Science
• Microbiology
• Pharmacology

Background:

• Atherosclerosis (AS) presents a significant global health challenge due to high morbidity and mortality.
• Bicyclol (BIC), a herb-derived compound, shows potential for AS treatment, but its efficacy requires investigation.

Purpose of the Study:

• To investigate the antiatherosclerotic effects of bicyclol (BIC).
• To elucidate the role of gut microbiota modulation in BIC's therapeutic mechanisms for AS.

Main Methods:

• Utilized Apoe^(-/-) mice fed a high-fat diet to model atherosclerosis.
• Employed metagenome-wide association studies to analyze gut microbiota composition and function.
• Assessed gut health, systemic immunity, liver function, and aortic arch pathology.
• Conducted fecal microbiota transplantation experiments to confirm therapeutic transmission.

Main Results:

• BIC normalized high-fat diet-induced gut dysbiosis in Apoe^(-/-) mice.
• BIC modulated carbohydrate-active and short-chain fatty acid-generating genes in gut flora.
• BIC intervention restored gut immunity and integrity, improving systemic immune cell dynamics and liver function.
• BIC alleviated endothelial activation, macrophage infiltration, and cholesterol accumulation in the aortic arch, reducing AS plaque.
• The antiatherosclerotic effects of BIC were transferable via fecal microbiota transplantation.

Conclusions:

• This study provides the first evidence of bicyclol's (BIC) antiatherosclerotic effects.
• BIC's therapeutic value in AS is significantly mediated by its positive modulation of gut microbiota.
• Targeting gut microbiota represents a promising therapeutic strategy for atherosclerosis management.