微生物衍生的尿性溶液增强宿主中血栓形成的潜力
Ina Nemet1,2, Masanori Funabashi3,4,5, Xinmin S Li1,2
1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA.
mBio
|November 10, 2023
概括
肠道微生物产生与心血管疾病相关的毒素. 我们确定了产生这些毒素的特定微生物基因,证明了它们在疾病风险和活体中促血栓状态中的作用.
科学领域:
- 微生物学 微生物学
- 心血管疾病研究研究
- 代谢学 代谢学 代谢学
背景情况:
- 肠道微生物代谢物越来越多地被认为对宿主健康和疾病的作用.
- 某些微生物产品的含量增加,如p-cresol硫酸盐和氧硫酸盐,与心血管疾病 (CVD) 风险增加有关.
- 了解产生这些有害分子的特定微生物通路对于开发向疗法至关重要.
研究的目的:
- 使用临床数据将微生物产品的血液水平与心血管疾病风险联系起来.
- 为了识别产生有害的尿素毒素的特定肠道微生物和酶.
- 在体内建立微生物基因,毒素生产和不良宿主表型之间的因果关系.
主要方法:
- 大规模的临床数据分析,以将微生物产品水平与心血管疾病风险和死亡率相关联.
- 甲基因组和酶分析以确定参与p-cresol和indole生产的微生物和基因.
- 没有细菌的小鼠模型被特定的微生物基因所定居,以评估体内毒素的形成和促血栓性影响.
主要成果:
- 临床观察将特定的微生物产品与心血管患者显著的5年死亡风险联系起来.
- 确定了产生p-cresol和indole的关键微生物基因,这些基因是p-cresol硫酸盐和indoxyl硫酸盐的前体.
- 证明这些微生物基因足以导致这些尿素毒素的形成,并在体内诱导一种促血栓性表型.
结论:
- 产生p-cresol和indole的肠道微生物通路直接与心血管疾病风险有关.
- 已识别的微生物基因和生物工程工具为治疗这些途径提供了基础.
- 这项研究确定了肠道微生物代谢,尿素毒素生产和心血管病理生理学之间的关键联系.
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