Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Canada; Dept. of Neurology, McMaster University, Hamilton, Canada.
Dept. Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Atherosclerosis. 2018 Jun;273:91-97. doi: 10.1016/j.atherosclerosis.2018.04.015. Epub 2018 Apr 17.
There is increasing awareness that the intestinal microbiome plays an important role in human health. We investigated its role in the burden of carotid atherosclerosis, measured by ultrasound as total plaque area.
Multiple regression with traditional risk factors was used to identify three phenotypes among 316/3056 patients attending vascular prevention clinics. Residual score (RES; i.e. the distance off the regression line, similar to standard deviation) was used to identify the 5% of patients with much less plaque than predicted by their risk factors (Protected, RES <-2), the 90% with about as much plaque as predicted (Explained, RES -2 to 2), and the 5% with much more plaque than predicted (Unexplained RES >2). Metabolic products of the intestinal microbiome that accumulate in renal failure - gut-derived uremic toxins (GDUT) - were assayed in plasma by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.
Plasma levels of trimethylamine n-oxide (TMAO), p-cresyl sulfate, p-cresyl glucuronide, and phenylacetylglutamine were significantly lower among patients with the Protected phenotype, and higher in those with the Unexplained phenotype, despite no significant differences in renal function or in dietary intake of nutrient precursors of GDUT. In linear multiple regression with a broad panel of risk factors, TMAO (p = 0.011) and p-cresyl sulfate (p = 0.011) were significant independent predictors of carotid plaque burden.
The intestinal microbiome appears to play an important role in atherosclerosis. These findings raise the possibility of novel approaches to treatment of atherosclerosis such as fecal transplantation and probiotics.
人们越来越意识到肠道微生物群在人类健康中起着重要作用。我们通过超声测量总斑块面积来研究其在颈动脉粥样硬化负担中的作用。
我们使用多元回归分析传统危险因素,在参加血管预防诊所的 316/3056 名患者中确定了三种表型。残余分数(RES;即离回归线的距离,类似于标准差)用于识别比其危险因素预测的斑块少得多的患者(保护,RES <-2)、与预测的斑块数量大致相同的患者(解释,RES -2 至 2)和比预测的斑块多得多的患者(未解释,RES >2)。通过超高效液相色谱-四极杆飞行时间质谱法测定在肾衰竭中积累的肠道微生物代谢产物-肠道来源的尿毒症毒素(GDUT)在血浆中的含量。
尽管肠道 GDUT 前体的膳食摄入量无明显差异,但在保护表型患者中,三甲胺 N-氧化物(TMAO)、对甲酚硫酸盐、对甲酚葡萄糖醛酸和苯乙酰谷氨酰胺的血浆水平明显较低,而在未解释表型患者中则较高。在包含广泛危险因素的线性多元回归中,TMAO(p=0.011)和对甲酚硫酸盐(p=0.011)是颈动脉斑块负担的独立显著预测因子。
肠道微生物群似乎在动脉粥样硬化中起着重要作用。这些发现提出了治疗动脉粥样硬化的新方法的可能性,例如粪便移植和益生菌。