Kumar Deepak, Bishnoi Mahendra, Kondepudi Kanthi Kiran, Sharma Shyam Sunder
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, 160062, India.
Centre for Excellence in Functional Foods, Division of Food and Nutritional Biotechnology, National Agri-Food Biomanufacturing Institute (NABI), Knowledge City-Sector 81, S.A.S. Nagar, Punjab, 140306, India.
Probiotics Antimicrob Proteins. 2025 Jan 15. doi: 10.1007/s12602-024-10433-x.
Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.
最近的证据表明肠道微生物群的改变与神经退行性疾病有关，包括帕金森病（PD）。通过基于肠道微生物群的干预措施“益生元、益生菌、合生元、后生元以及粪便微生物群移植（FMT）”来补充肠道微生物群的异常组成，已在帕金森病中显示出有益效果。这些干预措施会增加肠道代谢产物，如短链脂肪酸（SCFAs）和胰高血糖素样肽-1（GLP-1），它们可能通过肠-脑轴保护多巴胺能神经元。这些干预措施的神经保护作用是由多种机制介导的，包括神经营养因子的增强以及PI3K/AKT/mTOR信号通路的激活、GLP-1介导的肠-脑轴信号传导、Nrf2/ARE通路和自噬。其他途径，如游离脂肪酸受体激活、突触可塑性改善以及血脑屏障和肠道屏障完整性的维持，也有助于神经保护。此外，TLR4/NF-кB通路、MAPK通路、GSK-3β信号通路、miR-155-5p介导的神经炎症以及铁死亡的抑制也可能解释它们的保护作用。涉及基于肠道微生物群干预措施的临床研究已在帕金森病患者中显示出治疗益处，特别是在改善胃肠功能障碍和一些神经症状方面。然而，在缓解运动症状方面的效果仍然有限。仍需要大规模临床试验来证实这些发现。本综述强调了基于临床前和临床研究支持的肠道微生物群干预措施在帕金森病中的神经保护机制。
