Gut Microbiota-Derived Palmitic Acid Connects High-Fat Diets to Increased Blood Clot Risk

Recent research has unveiled a new connection between gut microbiota-produced palmitic acid (PA) and the heightened risk of blood clots associated with high-fat diets. Published in Cell Reports Medicine, this study highlights how a diet rich in fats can elevate circulating PA levels through gut bacteria, leading to a hypercoagulable state that raises cardiovascular disease (CVD) risk.

The researchers, including Prof. Lai Ren from the Kunming Institute of Zoology and Prof. Ni Heyu from the University of Toronto, observed that patients with cardiovascular issues exhibited significantly higher levels of circulating PA and a pronounced pro-coagulant tendency compared to healthy individuals. Notably, the abundance of Bacteroides thetaiotaomicron (BT) in the gut was approximately 2.18 times higher in the CVD group.

Further experiments revealed that PA inhibits activated protein C (APC), a crucial component of the body's anticoagulant system, thereby promoting blood clot formation. PA also enhances platelet activation, which can lead to thrombosis. These effects were confirmed through studies in mouse models. In vitro analysis identified BT strains capable of producing PA, and mice colonized with BT showed increased plasma PA levels and hypercoagulation, suggesting a causative role of gut microbes in thrombosis risk.

Diet plays a vital role in shaping the gut microbiome. The high-fat diet facilitated BT colonization, increased plasma PA, and induced hypercoagulability. Interestingly, the dietary bioflavonoid hesperidin was found to block the interaction between PA and APC, preventing the hypercoagulable state. This insight reveals a potential dietary intervention for reducing blood clot risks linked to high-fat diets.

Overall, this study proposes a novel mechanism linking diet, gut microbiota, and thrombosis, emphasizing the importance of gut microbial metabolites like PA in cardiovascular health. Managing dietary habits and exploring compounds like hesperidin could offer new approaches to mitigating CVD risk associated with gut microbiota activity.