Manfready Richard A, Engen Phillip A, Verhagen Metman Leo, Sanzo Gabriella, Goetz Christopher G, Hall Deborah A, Forsyth Christopher B, Raeisi Shohreh, Voigt Robin M, Keshavarzian Ali
Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States.
Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States.
Front Neurosci. 2021 Jul 2;15:660942. doi: 10.3389/fnins.2021.660942. eCollection 2021.
The incretin hormone glucagon-like peptide 1 (GLP-1) has neuroprotective effects in animal models of Parkinson's disease (PD), and GLP-1 receptor agonists are associated with clinical improvements in human PD patients. GLP-1 is produced and secreted by intestinal L-cells in response to consumption of a meal. Specifically, intestinal microbiota produce short chain fatty acids (SCFA) which, in turn, promote secretion of GLP-1 into the systemic circulation, from which it can enter the brain. Our group and others have reported that PD patients have an altered intestinal microbial community that produces less SCFA compared to age-matched controls. In this report, we demonstrate that PD patients have diminished GLP-1 secretion in response to a meal compared to their household controls. Peak postprandial GLP-1 levels did not correlate with PD disease severity, motor function, or disease duration. These data provide the scientific rationale for future studies designed to elucidate the role of GLP-1 in the pathogenesis of PD and test the potential utility of GLP-1-directed therapies.
肠促胰岛素胰高血糖素样肽1（GLP-1）在帕金森病（PD）动物模型中具有神经保护作用，且GLP-1受体激动剂与人类PD患者的临床改善相关。GLP-1由肠道L细胞在进食后产生并分泌。具体而言，肠道微生物群产生短链脂肪酸（SCFA），进而促进GLP-1分泌进入体循环，GLP-1可由此进入大脑。我们团队及其他研究团队均报告称，与年龄匹配的对照组相比，PD患者的肠道微生物群落发生改变，产生的SCFA较少。在本报告中，我们证明，与家庭对照组相比，PD患者进食后GLP-1分泌减少。餐后GLP-1峰值水平与PD疾病严重程度、运动功能或病程无关。这些数据为未来旨在阐明GLP-1在PD发病机制中的作用以及测试GLP-1导向疗法潜在效用的研究提供了科学依据。
