Vijay Amrita, Astbury Stuart, Panayiotis Louca, Marques Francine Z, Spector Tim D, Menni Cristina, Valdes Ana M
School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Department of Twin Research, King's College London, London, United Kingdom.
Front Cardiovasc Med. 2021 Jul 14;8:691564. doi: 10.3389/fcvm.2021.691564. eCollection 2021.
The current study investigates the role of diet in mediating the gut microbiome-cardiovascular association which has not yet been explored in humans. Using a two-arm dietary intervention study in healthy participants ( = 70), we assessed the effects of omega-3 and fibre supplementation on gut microbiome composition and short-chain fatty acid (SCFA) production. We then investigated how changes in gut microbiome composition correlated with changes in traditional cardiovascular risk factors (cholesterol, triglycerides, blood pressure), cytokines, and novel validated markers such as GlycA and ceramides, previously linked to CVD incidence and mortality. Both interventions resulted in significant drops in blood pressure, cholesterol, proinflammatory cytokines, GlycA and ceramides (all < 0.05). Decreases in the atherogenic low-density lipoprotein triglyceride fraction, in total serum cholesterol were correlated with increases in butyric acid-production [β(SE) = -0.58 (0.06), < 0.001; -0.53 (0.04), < 0.001] and nominally associated with increases in some butyrogenic bacteria. Drops in GlycA were linked to increases in [β(SE) = -0.32 (0.04), = 0.02] and other SCFAs including acetic acid [β(SE) = -0.28 (0.04), = 0.02] and propionic acid [β(SE) = -0.3 (0.04), = 0.02]. Additionally, we report for the first-time reductions in specific ceramide ratios that have been shown to predict CVD mortality and major adverse cardiovascular events such as d18:1/16:0, d18:0/24:0, and d18:1/24:1 which were associated with the reduction in the abundance in and increases in and and SCFAs (all < 0.05). Overall, these findings support the potential of using simple dietary interventions to alter validated biomarkers linked to cardiovascular risk via the gut microbiome composition and its metabolic functions.
本研究调查了饮食在介导肠道微生物群与心血管关联中的作用，这在人类中尚未得到探索。我们在70名健康参与者中进行了一项双臂饮食干预研究，评估了补充ω-3脂肪酸和膳食纤维对肠道微生物群组成和短链脂肪酸（SCFA）产生的影响。然后，我们研究了肠道微生物群组成的变化与传统心血管危险因素（胆固醇、甘油三酯、血压）、细胞因子以及新验证的标志物（如GlycA和神经酰胺）的变化之间的相关性，这些标志物此前与心血管疾病的发病率和死亡率有关。两种干预措施均导致血压、胆固醇、促炎细胞因子、GlycA和神经酰胺显著下降（均P<0.05）。致动脉粥样硬化的低密度脂蛋白甘油三酯部分和总血清胆固醇的降低与丁酸产生的增加相关[β（标准误）=-0.58（0.06），P<0.001；-0.53（0.04），P<0.001]，并且与一些产丁酸细菌的增加存在名义上的关联。GlycA的下降与戊酸[β（标准误）=-0.32（0.04），P=0.02]以及包括乙酸[β（标准误）=-0.28（0.04），P=0.02]和丙酸[β（标准误）=-0.3（0.04），P=0.02]在内的其他SCFAs的增加有关。此外，我们首次报告了特定神经酰胺比例的降低，这些比例已被证明可预测心血管疾病死亡率和主要不良心血管事件，如d18:1/16:0、d18:0/24:0和d18:1/24:1，它们与拟杆菌属丰度的降低以及双歧杆菌属和粪杆菌属以及SCFAs的增加相关（均P<0.05）。总体而言，这些发现支持了通过简单的饮食干预来改变与心血管风险相关的已验证生物标志物的潜力，这种改变是通过肠道微生物群组成及其代谢功能实现的。
