Huang Xiaoshan, Tang Xiaopeng, He Qiuyue, Tadese Dawit Adisu, Cao Kaixun, Gao Jinai, Xu Qiuyue, Cheng Ruomei, Lu Qiumin, Chen Yifan, Yang Min, Du Yan, Mwangi James, Ni Heyu, Lai Ren
KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan 650201, P.R. China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan 650201, P.R. China.
Cell Rep Med. 2025 Aug 19;6(8):102260. doi: 10.1016/j.xcrm.2025.102260. Epub 2025 Jul 31.
Circulating palmitic acid (PA) is generally considered to be provided from diets and endogenous synthesis and is adversely correlated with cardiovascular disease (CVD). It is unknown, however, if gut microbiota modulates circulating PA and potentiates CVD risk. Here we demonstrate that, in CVD patients, elevated circulating PA is accompanied with hypercoagulability and high gut Bacteroides thetaiotaomicron (BT) abundance. PA promotes coagulation by inhibiting a major endogenous anticoagulant activated protein C (APC) and enhancing platelet activation. Importantly, BT is capable of synthesizing PA, and high-fat diet amplifies gut BT colonization. Our findings show that BT transplantation elevates plasma PA and triggers hypercoagulation without alternating host lipogenesis. Hesperidin, a dietary flavonoid, inhibits PA-APC interaction to prevent hypercoagulation induced by PA or BT transplantation. Collectively, we reveal the promotion of high-fat diet on gut BT colonization that elevates circulating PA and CVD risk, suggesting an approach controlling CVD by targeting PA and BT.
循环中的棕榈酸（PA）通常被认为来自饮食和内源性合成，并且与心血管疾病（CVD）呈负相关。然而，肠道微生物群是否调节循环中的PA并增加CVD风险尚不清楚。在这里，我们证明，在CVD患者中，循环PA升高伴随着高凝状态和肠道嗜热栖粪杆菌（BT）丰度增加。PA通过抑制主要的内源性抗凝剂活化蛋白C（APC）并增强血小板活化来促进凝血。重要的是，BT能够合成PA，高脂饮食会增加肠道BT定植。我们的研究结果表明，BT移植会升高血浆PA并引发高凝状态，而不会改变宿主脂肪生成。橙皮苷是一种膳食黄酮类化合物，可抑制PA-APC相互作用，以防止PA或BT移植诱导的高凝状态。总的来说，我们揭示了高脂饮食对肠道BT定植的促进作用，这会升高循环PA和CVD风险，提示了一种通过靶向PA和BT来控制CVD的方法。
