摘要
      第二种最常见的神经退行性疾病，帕金森病（PD），以运动和非运动症状为特征。左旋多巴是目前治疗帕金森病的支柱。然而，左旋多巴引起的副作用，如运动障碍，在帕金森病患者中很常见。最近，人们发现几种抗生素对神经退行性和神经炎症过程具有神经保护作用，这可能被开发为对帕金森病的有效治疗方法。在本研究中，我们旨在确定左旋多巴治疗是否会影响帕金森病大鼠的肠道细菌抗生素耐药性。从不同剂量左旋多巴治疗的健康大鼠和6-OHDA诱导的PD大鼠身上采集粪便样本，宏基因组测序数据显示左旋多巴导致肠道细菌组成变化，LEfSe分析的肠道细菌生物标志物也发生了变化。更有趣的是，与左旋多巴（5 mg/kg）治疗或不治疗左旋多巴的PD大鼠，左旋多巴（10 mg/kg）导致肠道细菌中tetW和vanTG基因的丰度显著降低，这与四环素和万古霉素耐药性有关，而AAC6 lb Suzhou基因的丰度明显增加，这与氨基糖苷类耐药性有关，尽管所有组之间的抗生素耐药性基因（ARG）和抗生素耐药性本体论（ARO）的总量没有显著差异。因此，我们的研究结果表明，左旋多巴与四环素和万古霉素等抗生素联合治疗帕金森病可能会减少肠道细菌中相应抗生素耐药性基因的数量，这将为未来左旋多巴联合四环素和万古霉素治疗帕金森病提供理论依据。
Abstract
The second most prevalent neurodegenerative ailment, Parkinson’s disease (PD), is characterized by both motor and non-motor symptoms. Levodopa is the backbone of treatment for PD at the moment. However, levodopa-induced side effects, such as dyskinesia, are commonly seen in PD patients. Recently, several antibiotics were found to present neuroprotective properties against neurodegenerative and neuro-inflammatory processes, which might be developed to effective therapies against PD. In this study, we aimed to identify if levodopa treatment could influence the gut bacterial antibiotic resistance in PD rat. Fecal samples were collected from healthy rats and 6-OHDA induced PD rats treated with different doses of levodopa, metagenomic sequencing data showed that levodopa resulted in gut bacteria composition change, the biomarkers of gut bacteria analyzed by LEfSe changed as well. More interestingly, compared with levodopa (5 mg/kg)-treated or no levodopa-treated PD rats, levodopa (10 mg/kg) caused a significant decrease in the abundance of tetW and vanTG genes in intestinal bacteria, which were related to tetracycline and vancomycin resistance, while the abundance of AAC6-lb-Suzhou gene increased apparently, which was related to aminoglycosides resistance, even though the total quantity of Antibiotic Resistance Gene (ARG) and Antibiotic Resistance Ontology (ARO) among all groups did not significantly differ. Consequently, our results imply that the combination of levodopa and antibiotics, such as tetracycline and vancomycin, in the treatment of PD may decrease the amount of corresponding antibiotic resistance genes in gut bacteria, which would give a theoretical basis for treating PD with levodopa combined with tetracycline and vancomycin in the future.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941341/