Gut Bacteria May Keep Statin Response in Check By Todd Neale, Senior Staff Writer, MedPage Today Published: October 16, 2011 Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. http://www.medpagetoday.com/Cardiology/Dyslipidemia/29067?pfc=121&spc=234 研究人员指出，许多在胆汁中的细菌丛会影响 statin 药物的治疗成效。 Various bacterial-derived bile acids appear to influence the response to statin treatment, researchers found. 根据 Rima Kaddurah-Daouk 在健康的受试者发现，於治疗前的初级及次级胆酸浓度与 simvastatin 降LDL-C 的成效具有强烈的相关性。 Pretreatment levels of several primary and secondary bile acids were strongly associated with the low-density lipoprotein (LDL) cholesterol- lowering ability of simvastatin in healthy individuals, according to Rima Kaddurah-Daouk, PhD, of Duke University, and colleagues. 研究人员指出：「肠道中的微生物菌丛是否能作为statins药物的治疗反应之特异性指 标，需要进一步的观察及证实。」「若能厘清其间的相关性，那麽我们或许可以藉由 饮食等方面改变肠道的菌丛，从而提高 statins 药物之治疗成效。」 The findings, reported online in PLoS ONE, "warrant further evaluation of interactions of specific markers for gut microbiota and therapeutic response to statins," the researchers wrote. "Identification of the basis for such interactions may in turn lead to dietary or other interventions that can improve statin efficacy by altering gut microflora." 实际上在个体间有许多差异都可能影响到 statin 的药效，如基因便是其一。 [译者按：] Atorvastatin vs. HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 -DNA Cell Biol. 2010 Oct;29(10):629-37. Atorvastatin vs. CYP7A1 A-204C and ABCG8 C1199A -J Clin Pharm Ther. 2010 Dec 3. doi: 10.1111/j.1365-2710.2010.01227.x. Statins vs. SLCO1B1, APO-E and CETP, et al. -Drug Saf. 2011 Jan 1;34(1):1-19. -Pharmacogenomics J. 2010 Feb;10(1):1-11. Epub 2009 Nov 3. There is variability among individuals in the therapeutic response to statins, and previous studies have shown that genetics can only account for part of it. Kaddurah-Daouk等人结合了代谢体领域的研究者，探讨包括基因体、微生物学和治疗 环境间对疗效的交互作用。 Kaddurah-Daouk and colleagues turned to the field of metabolomics, which incorporates the interactions between a person's genome, microbiome, and environment in explaining response to treatments. 研究人员将自胆固醇研究与药物基因学研究中的受试者分为两个族群，以探讨可能可 以帮助预测statin治疗成效的生物指标。设计将这些之前未服用任何药物的健康受试 者每天服用 simvastatin 40 mg 共六个礼拜，以观察其治疗成效。 To search for biomarkers that might help predict response to statin therapy, the researchers used two groups of participants from the Cholesterol and Pharmacogenetics Study. The latter was designed to identify factors related to the response to six weeks of treatment with simvastatin 40 mg in healthy, drug-naive volunteers. 第一组随机收纳了100位受试者，并以其接受治疗後LDL-C所降数值之范围作为全距组。 One group consisted of 100 randomly selected individuals across the spectrum of LDL cholesterol-lowering response to statin therapy and constituted the full-range group. 由statin治疗成效中挑选最好和最差各24人作为第二组 (48人)。 The second group was made up of 48 individuals -- 24 from the top 10% and 24 from the bottom 10% in terms of response to statin therapy, who were the good and poor performers, respectively. 研究人员对这些受试者进行代谢体学的评估分析，包含其代谢物与 cholesterol 合成 、饮食中固醇类物质的吸收，以及胆酸形成之相关性。 In all of these participants, the researchers used a metabolomics platform to measure a panel of metabolites related to cholesterol synthesis, dietary sterol absorption, and bile acid formation. 在全距组的资料显示，在治疗前此五种初级与次级胆酸物质之浓度越低，对 simvastatin治疗成效越好 (p<0.02 for all)。 - Taurocholic acid (TCA) - Glycocholic acid (GCA) - Taurochenodeoxycholic acid (TCDCA) - Glycochenodeoxycholic acid (GCDCA) - Glycoursodeoxycholic acid (GUDCA) In the full-range group, there was a correlation between lower pretreatment levels of five primary and secondary bile acids: - Taurocholic acid (TCA) - Glycocholic acid (GCA) - Taurochenodeoxycholic acid (TCDCA) - Glycochenodeoxycholic acid (GCDCA) - Glycoursodeoxycholic acid (GUDCA) The full-range group had a greater LDL cholesterol-lowering response to simvastatin (P<0.02 for all). 在48人组的分析中显示，在治疗前 lithocholic acid (LCA), taurolithocholic acid (TLCA)和glycolithocholicacid (GLCA) 此三种次级胆酸产物的浓度越高， 则对statin的治疗成效越好 (p<0.05 for all)。而这些次级胆酸产物皆是由肠道 中之细菌所制造的。 In the good and poor responders, higher pretreatment levels of three secondary bile acids -- lithocholic acid (LCA), taurolithocholic acid (TLCA), and glycolithocholic acid (GLCA) -- were associated with a better response to statin therapy (P<0.05 for all). These secondary bile acids are produced by intestinal bacteria. 胆酸与statins在肝脏、肠道中均藉由相同转运蛋白的作用，研究人员指出，实验 显示在这些具有较高血中浓度之simvastatin的受试者，与具有较高次级胆酸产物 浓度存在相关性。 Bile acids and statins use the same transporters in the liver and intestine, and the researchers observed that an increased plasma concentration of simvastatin was associated with higher levels of several secondary bile acids in the study groups. Kaddurah-Daouk表示：「目前已知胆酸在内分泌讯息、身体系统性调控脂肪浓度之 功能、肌肉功能以及免疫细胞的调节扮演着重要的脚色。」「然而它依然逃不过我 们的法眼(误)，我们发现胆酸可能对statin的影响可能包括了治疗效果和副作用等 ，显示胆酸对於statin活性的调控是非常重要的。」 "Bile acids are known to be important endocrine signals, functioning in the systemic control of lipid levels, muscle function, and immune cell regulation," the authors wrote. "It has not escaped our attention that all of these pathways are affected by statins, either as therapeutic targets or side effects, suggesting that bile acids may be important mediators of statin activities." 「近来，也有许多研究证实，肠道中的菌丛在心血管疾病中可能占有重要的脚色， 而我们的研究发现基因体、肠道菌丛与生理环境之交互作用所造成的影响，或许也 能应用於对心血管疾病之治疗上。」 They concluded that the findings, "along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome, and environmental influences should be considered in the study and management of cardiovascular disease." Kaddurah-Daouk也提到：「本研究结果仅能应用於simvastatin上，而其他statin 之机转或许与之不同，仍待其他研究证实、厘清。」 The investigators noted that their results could only be applied to simvastatin as metabolites and pathways for other statins might differ. Primary source: PLoS ONE Source reference: Kaddurah-Daouk R, et al "Enteric microbiome metabolites correlate with response to simvastatin treatment" PLoS ONE 2011; DOI:10.1371/journal.pone.0025482. http://www.medpagetoday.com/Cardiology/Dyslipidemia/29067?pfc=121&spc=234 -- ψjpg10330 ◢ ▄ ◣ God bless you. 宽恕是病人与上帝的事 我的工作是安排他们见面 ▁▂▄▂▁/ ◣ Bible ◎..◎ \ ▁▄▅▃▂ by 波波 ︵ ▏ +◣ ◣ ▅▆ ▇▆▅▆ ◣ ◣◣ ◣ ︶ ◢ ◢◤ ∵ ▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄▄ ◥ ▇﹨ 〒 ∕▇ ◤ --

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