Sancandi Marco, De Caro Carmen, Cypaite Neringa, Marascio Nadia, Avagliano Carmen, De Marco Carmela, Russo Emilio, Constanti Andrew, Mercer Audrey
Department of Pharmacology, UCL School of Pharmacy, London, United Kingdom.
Department of Science of Health, School of Medicine, University of Catanzaro, Catanzaro, Italy.
Front Aging Neurosci. 2023 Jan 18;14:986127. doi: 10.3389/fnagi.2022.986127. eCollection 2022.
An increasing number of studies in recent years have focused on the role that the gut may play in Parkinson's Disease (PD) pathogenesis, suggesting that the maintenance of a healthy gut may lead to potential treatments of the disease. The health of microbiota has been shown to be directly associated with parameters that play a potential role in PD including gut barrier integrity, immunity, function, metabolism and the correct functioning of the gut-brain axis. The gut microbiota (GM) may therefore be employed as valuable indicators for early diagnosis of PD and potential targets for preventing or treating PD symptoms. Preserving the gut homeostasis using probiotics may therefore lead to a promising treatment strategy due to their known benefits in improving constipation, motor impairments, inflammation, and neurodegeneration. However, the mechanisms underlying the effects of probiotics in PD are yet to be clarified. In this project, we have tested the efficacy of an oral probiotic suspension, Symprove™, on an established animal model of PD. Symprove™, unlike many commercially available probiotics, has been shown to be resistant to gastric acidity, improve symptoms in gastrointestinal diseases and improve gut integrity in an PD model. In this study, we used an early-stage PD rat model to determine the effect of Symprove™ on neurodegeneration and neuroinflammation in the brain and on plasma cytokine levels, GM composition and short chain fatty acid (SCFA) release. Symprove™ was shown to significantly influence both the gut and brain of the PD model. It preserved the gut integrity in the PD model, reduced plasma inflammatory markers and changed microbiota composition. The treatment also prevented the reduction in SCFAs and striatal inflammation and prevented tyrosine hydroxylase (TH)-positive cell loss by 17% compared to that observed in animals treated with placebo. We conclude that Symprove™ treatment may have a positive influence on the symptomology of early-stage PD with obvious implications for the improvement of gut integrity and possibly delaying/preventing the onset of neuroinflammation and neurodegeneration in human PD patients.
近年来，越来越多的研究聚焦于肠道在帕金森病（PD）发病机制中可能发挥的作用，这表明维持肠道健康可能为该疾病带来潜在的治疗方法。微生物群的健康已被证明与在PD中发挥潜在作用的参数直接相关，这些参数包括肠道屏障完整性、免疫、功能、代谢以及肠脑轴的正常运作。因此，肠道微生物群（GM）可用作PD早期诊断的有价值指标以及预防或治疗PD症状的潜在靶点。由于益生菌在改善便秘、运动障碍、炎症和神经退行性变方面具有已知的益处，因此使用益生菌维持肠道稳态可能会带来一种有前景的治疗策略。然而，益生菌在PD中的作用机制尚待阐明。在本项目中，我们测试了口服益生菌悬液Symprove™对已建立的PD动物模型的疗效。与许多市售益生菌不同，Symprove™已被证明对胃酸具有抗性，可改善胃肠道疾病症状并改善PD模型中的肠道完整性。在本研究中，我们使用早期PD大鼠模型来确定Symprove™对大脑神经退行性变和神经炎症以及血浆细胞因子水平、GM组成和短链脂肪酸（SCFA）释放的影响。结果表明，Symprove™对PD模型的肠道和大脑均有显著影响。它维持了PD模型中的肠道完整性，降低了血浆炎症标志物水平并改变了微生物群组成。与接受安慰剂治疗的动物相比，该治疗还防止了SCFAs的减少和纹状体炎症，并防止酪氨酸羟化酶（TH）阳性细胞损失17%。我们得出结论，Symprove™治疗可能对早期PD的症状学产生积极影响，这对改善肠道完整性以及可能延迟/预防人类PD患者神经炎症和神经退行性变的发生具有明显意义。
