肠道菌群调控或可降低衰老相关的心血管疾病风险
创作:徐笑 审核:szx 2019年03月28日
  • 动脉功能障碍表现为氧化应激和炎症介导的内皮功能障碍和动脉硬化,与年龄相关;
  • 随年龄增长,菌群丰度改变导致肠道菌群失调,引起氧化应激,并增加血浆中的氧化三甲胺水平;
  • 广谱抗生素治疗3-4周可逆转老龄小鼠内皮功能障碍和动脉硬化,减轻了血管氧化应激和炎症,伴随促炎细胞因子浓度降低、氧化应激减弱和大量抗氧化酶表达;
  • 肠道菌群是老年动脉功能障碍的重要媒介,维持肠道菌群健康或能降低老年心血管患病的风险。
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《Journal of Physiology》上发表的一项最新研究,发现在老龄小鼠中,广谱抗生素处理可逆转其动脉功能障碍,同时降低肠道菌群代谢产物氧化三甲胺的水平,提示肠道菌群在衰老相关的动脉功能障碍中发挥重要作用,靶向调控菌群或可降低老年人的心血管疾病风险。
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Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice

抑制肠道菌群可缓解小鼠衰老相关的动脉功能障碍和氧化应激

10.1113/JP277336

2019-02-04, Article

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KEY POINTS: Age-related arterial dysfunction, characterized by oxidative stress- and inflammation-mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for cardiovascular diseases. To investigate whether age-related changes in the gut microbiome may mediate arterial dysfunction, we suppressed gut microbiota in young and old mice with a cocktail of broad-spectrum, poorly-absorbed antibiotics in drinking water for 3-4 weeks. In old mice, antibiotic treatment reversed endothelial dysfunction and arterial stiffening and attenuated vascular oxidative stress and inflammation. To provide insight into age-related changes in gut microbiota that may underlie these observations, we show that ageing altered the abundance of microbial taxa associated with gut dysbiosis and increased plasma levels of the adverse gut-derived metabolite trimethylamine N-oxide. The results of the present study provide the first proof-of-concept evidence that the gut microbiome is an important mediator of age-related arterial dysfunction and therefore may be a promising therapeutic target for preserving arterial function with ageing, thereby reducing the risk of cardiovascular diseases.
ABSTRACT: Oxidative stress-mediated arterial dysfunction (e.g. endothelial dysfunction and large elastic artery stiffening) is the primary mechanism driving age-related cardiovascular diseases. Accumulating evidence suggests the gut microbiome modulates host physiology because dysregulation ('gut dysbiosis') has systemic consequences, including promotion of oxidative stress. The present study aimed to determine whether the gut microbiome modulates arterial function with ageing. We measured arterial function in young and older mice after 3-4 weeks of treatment with broad-spectrum, poorly-absorbed antibiotics to suppress the gut microbiome. To identify potential mechanistic links between the gut microbiome and age-related arterial dysfunction, we sequenced microbiota from young and older mice and measured plasma levels of the adverse gut-derived metabolite trimethylamine N-oxide (TMAO). In old mice, antibiotics reversed endothelial dysfunction [area-under-the-curve carotid artery dilatation to acetylcholine in young: 345 ± 16 AU vs. old control (OC): 220 ± 34 AU, P < 0.01; vs. old antibiotic-treated (OA): 334 ± 15 AU; P < 0.01 vs. OC] and arterial stiffening (aortic pulse wave velocity in young: 3.62 ± 0.15 m s vs. OC: 4.43 ± 0.38 m s ; vs. OA: 3.52 ± 0.35 m s ; P = 0.03). These improvements were accompanied by lower oxidative stress and greater antioxidant enzyme expression. Ageing altered the abundance of gut microbial taxa associated with gut dysbiosis. Lastly, plasma TMAO was higher with ageing (young: 2.6 ± 0.4 μmol L   vs. OC: 7.2 ± 2.0 μmol L ; P < 0.0001) and suppressed by antibiotic treatment (OA: 1.2 ± 0.2 μmol L ; P < 0.0001 vs. OC). The results of the present study provide the first evidence for the gut microbiome being an important mediator of age-related arterial dysfunction and oxidative stress and suggest that therapeutic strategies targeting gut microbiome health may hold promise for preserving arterial function and reducing cardiovascular risk with ageing in humans.

First Authors:
Vienna E Brunt

Correspondence Authors:
Vienna E Brunt

All Authors:
Vienna E Brunt,Rachel A Gioscia-Ryan,James J Richey,Melanie C Zigler,Lauren M Cuevas,Antonio Gonzalez,Yoshiki Vázquez-Baeza,Micah L Battson,Andrew T Smithson,Andrew D Gilley,Gail Ackermann,Andrew P Neilson,Tiffany Weir,Kevin P Davy,Rob Knight,Douglas R Seals

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