From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.).
Department of Pediatrics (N.S.), Medical College of Wisconsin, Milwaukee.
Circ Res. 2018 Oct 12;123(9):1091-1102. doi: 10.1161/CIRCRESAHA.118.313565.
A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature.
To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD).
Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes.
Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study.
URL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.
肠道微生物群与动脉粥样硬化疾病之间存在很强的关联。我们最近的数据表明，植物乳杆菌 299v（Lp299v）补充剂可减少雄性大鼠的梗死面积。关于 Lp299v 对血管的影响，目前仅有有限的人类数据。
确定口服 Lp299v 补充剂是否可改善稳定型冠状动脉疾病（CAD）患者的血管内皮功能并减轻全身炎症。
20 名患有稳定型 CAD 的男性每天饮用一次含有 Lp299v（200 亿 CFU）的饮料，持续 6 周。经过 4 周的洗脱期后，受试者可选择再参加为期 10 天的口服万古霉素（250 mg QID）研究。通过肱动脉血流介导的扩张来测量血管内皮功能。在 Lp299v 补充前后，测量血浆短链脂肪酸、氧化三甲胺和脂肪因子水平。使用液相色谱/质谱联用技术对其他血浆样本进行无偏代谢组学分析。使用 16S rRNA 测序确定粪便微生物组的变化。从 CAD 患者中获得小动脉，并在经腔内孵育来自 Lp299v 研究受试者的血浆后，通过视频显微镜测量内皮依赖性血管舒张。Lp299v 补充可改善肱动脉血流介导的扩张（P=0.008），而血浆胆固醇谱、空腹血糖或体重指数无明显变化。万古霉素对血流介导的扩张没有影响。Lp299v 补充可降低循环白细胞介素（IL）-8（P=0.01）、IL-12（P=0.02）和瘦素（P=0.0007）水平，但对血浆氧化三甲胺浓度无显著影响（P=0.27）。血浆丙酸盐（P=0.004）增加，而乙酸盐水平降低（P=0.03）。Lp299v 后血浆可改善 CAD 患者阻力动脉的内皮依赖性血管舒张（P=0.02）。16S rRNA 分析显示，在益生菌后粪便样本中乳杆菌属丰富，而无其他变化。
Lp299v 可改善 CAD 男性的血管内皮功能并减轻全身炎症，而与传统危险因素和氧化三甲胺无关。循环肠道来源的代谢物可能是这些改善的原因，值得进一步研究。
