对莱沃多巴代谢的跨物种肠道细菌途径的发现和抑制
Vayu Maini Rekdal1, Elizabeth N Bess2,3,4, Jordan E Bisanz2
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|June 15, 2019
概括
肠道微生物通过特定的细菌酶代谢帕金森病药物莱沃多巴 (l-多巴). 发现一种新型抑制剂可以阻断这种新陈代谢,从而增加小鼠的药物生物可用性.
科学领域:
- 微生物学
- 药理学
- 神经科学
背景情况:
- 肠道微生物群对利沃多巴 (l-多巴) 的代谢有显著影响,利沃多巴是帕金森病的主要药物.
- 这种微生物代谢可以降低药物的疗效并加剧副作用,但具体机制尚不清楚.
研究的目的:
- 阐明参与肠道微生物群中介的利沃多巴代谢的细菌生物,基因和酶.
- 研究抑制这些微生物酶以改善莱沃多巴的生物可用性.
主要方法:
- 描述了细菌莱沃多巴代谢的跨物种途径.
- 确定了关键酶:来自Enterococcus faecalis的氨酸脱酶和来自Eggerthella lenta的脱酶.
- 使用针对宿主药物和新型化合物测试了微生物Levodopa代谢的抑制.
主要成果:
- 描述了一种涉及*E. faecalis*和*E. lenta*的两步路径,用于将Levodopa转化为多巴胺,然后转化为*m*- tyramine.
- 证明针对宿主的药物对微生物的利沃多巴代谢无效.
- 在帕金森病患者的微生物体中抑制了微生物的利沃多巴代谢,并提高了小鼠的利沃多巴生物可用性.
结论:
- 已确定的细菌酶和途径对肠道中的利沃多巴代谢至关重要.
- 针对微生物酶,而不是宿主酶,提供了一种有前途的策略来增强利沃多巴治疗.
- 一种新型的抑制剂有望改善帕金森病患者的利沃多巴生物可用性.
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