Association of Enterococcus faecalis and tyrosine decarboxylase gene levels with levodopa pharmacokinetics in Parkinson’s disease

IF 8.2 1区医学 Q1 NEUROSCIENCES NPJ Parkinson's Disease Pub Date : 2025-03-18 DOI:10.1038/s41531-025-00903-6

Noriyuki Miyaue, Haruto Yamamoto, Shuang Liu, Yuko Ito, Yuki Yamanishi, Rina Ando, Yasuyuki Suzuki, Masaki Mogi, Masahiro Nagai

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Abstract

Multiple factors affect the absorption of orally administered levodopa, the gold standard for the treatment of Parkinson’s disease (PD). Enterococcus faecalis (E. faecalis) expresses the enzyme tyrosine decarboxylase (tyrDC), which metabolizes levodopa into dopamine and thereby may influence its absorption in patients with PD. This study investigated the association between fecal E. faecalis and tyrDC gene levels and the pharmacokinetics of orally administered levodopa in 21 patients with PD. Our results revealed a significant association between elevated fecal levels of E. faecalis and tyrDC gene levels and reduced peak plasma levodopa concentrations. Additionally, among patients receiving levodopa-carbidopa intestinal gel treatment, strong positive correlations were observed between E. faecalis and tyrDC gene levels in fecal samples and those from the tip of the jejunal tube. Further prospective studies are required to explore the potential role of gut microbiota as a therapeutic target in patients with PD.

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粪肠球菌和酪氨酸脱羧酶基因水平与帕金森病患者左旋多巴药代动力学的关系

多种因素影响口服左旋多巴的吸收，左旋多巴是治疗帕金森病（PD）的金标准。粪肠球菌（E. faecalis）表达酪氨酸脱羧酶（tyrDC），将左旋多巴代谢为多巴胺，从而可能影响PD患者对多巴胺的吸收。本研究探讨了21例PD患者粪便中粪肠杆菌和tyrDC基因水平与口服左旋多巴药代动力学的关系。我们的研究结果揭示了粪肠杆菌水平升高与tyrDC基因水平和血浆左旋多巴浓度峰值降低之间的显著关联。此外，在接受左旋多巴-卡比多巴肠道凝胶治疗的患者中，粪便样本和空肠管尖端的粪肠杆菌和tyrDC基因水平呈强正相关。需要进一步的前瞻性研究来探索肠道微生物群作为PD患者治疗靶点的潜在作用。

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来源期刊

NPJ Parkinson's Disease Medicine-Neurology (clinical)

CiteScore

9.80

自引率

5.70%

发文量

156

审稿时长

11 weeks

期刊介绍： npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.