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DOI | 10.1038/s41467-017-00669-3 |
Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease | |
van Kessel, Sebastiaan P.1; Frye, Alexandra K.1; El-Gendy, Ahmed O.1,4; Castejon, Maria1; Keshavarzian, Ali2; van Dijk, Gertjan3; El Aidy, Sahar1 | |
2019-01-18 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Netherlands; USA; Egypt |
英文摘要 | Human gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a competitive substrate, or inhibitors of human decarboxylase. In situ levels of levodopa are compromised by high abundance of gut bacterial tyrosine decarboxylase in patients with Parkinson's disease. Finally, the higher relative abundance of bacterial tyrosine decarboxylases at the site of levodopa absorption, proximal small intestine, had a significant impact on levels of levodopa in the plasma of rats. Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson's disease patients. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000456010800007 |
WOS关键词 | INTESTINAL MICROBIOTA ; L-DOPA ; EXPRESSION ; OVERGROWTH ; METABOLISM ; HOST ; PCR |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203431 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Groningen, Groningen Biomol Sci & Biotechnol Inst GBB, Dept Mol Immunol & Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands; 2.Rush Univ, Div Digest Dis & Nutr, Sect Gastroenterol, Dept Internal Med,Med Ctr, 1725 W Harrison,Suite 206, Chicago, IL 60612 USA; 3.Univ Groningen, Groningen Inst Evolutionary Life Sci GELIFES, Dept Behav Neurosci, Nijenborgh 7, NL-9747 AG Groningen, Netherlands; 4.Beni Suef Univ, Dept Microbiol & Immunol, Fac Pharm, Bani Suwayf 62514, Egypt |
推荐引用方式 GB/T 7714 | van Kessel, Sebastiaan P.,Frye, Alexandra K.,El-Gendy, Ahmed O.,et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease[J]. NATURE COMMUNICATIONS,2019,10. |
APA | van Kessel, Sebastiaan P..,Frye, Alexandra K..,El-Gendy, Ahmed O..,Castejon, Maria.,Keshavarzian, Ali.,...&El Aidy, Sahar.(2019).Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease.NATURE COMMUNICATIONS,10. |
MLA | van Kessel, Sebastiaan P.,et al."Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease".NATURE COMMUNICATIONS 10(2019). |
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