Elford Joshua D, Becht Nanette, Garssen Johan, Kraneveld Aletta D, Perez-Pardo Paula
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Danone Nutricia Research, Utrecht, Netherlands.
Front Pharmacol. 2024 Apr 17;15:1388401. doi: 10.3389/fphar.2024.1388401. eCollection 2024.
Parkinson's disease (PD) is a complex neurodegenerative disease which is often associated with gastrointestinal (GI) dysfunction. The GI tract is home to a wide range of microorganisms, among which bacteria, that can influence the host through various mechanisms. Products produced by these bacteria can act in the gut but can also exert effects in the brain via what is now well established to be the microbiota-gut-brain axis. In those with PD the gut-bacteria composition is often found to be different to that of non-PD individuals. In addition to compositional changes, the metabolic activity of the gut-microbiota is also changed in PD. Specifically, it is often reported that key producers of short chain fatty acids (SCFAs) as well as the concentration of SCFAs themselves are altered in the stool and blood of those with PD. These SCFAs, among which butyrate, are essential nutrients for the host and are a major energy source for epithelial cells of the GI tract. Additionally, butyrate plays a key role in regulating various host responses particularly in relation to inflammation. Studies have demonstrated that a reduction in butyrate levels can have a critical role in the onset and progression of PD. Furthermore, it has been shown that restoring butyrate levels in those with PD through methods such as probiotics, prebiotics, sodium butyrate supplementation, and fecal transplantation can have a beneficial effect on both motor and non-motor outcomes of the disease. This review presents an overview of evidence for the altered gut-bacteria composition and corresponding metabolite production in those with PD, with a particular focus on the SCFA butyrate. In addition to presenting current studies regarding SCFA in clinical and preclinical reports, evidence for the possibility to target butyrate production using microbiome based approaches in a therapeutic context is discussed.
帕金森病(PD)是一种复杂的神经退行性疾病,常与胃肠(GI)功能障碍相关。胃肠道是多种微生物的家园,其中细菌可通过多种机制影响宿主。这些细菌产生的产物可在肠道发挥作用,但也可通过现已明确的微生物群-肠-脑轴在大脑中产生影响。在帕金森病患者中,肠道细菌组成通常与非帕金森病个体不同。除了组成变化外,帕金森病患者的肠道微生物群代谢活性也发生了改变。具体而言,经常有报道称,帕金森病患者粪便和血液中短链脂肪酸(SCFA)的关键产生者以及SCFA本身的浓度发生了改变。这些SCFA,其中包括丁酸盐,是宿主的必需营养素,也是胃肠道上皮细胞的主要能量来源。此外,丁酸盐在调节各种宿主反应,特别是与炎症相关的反应中起关键作用。研究表明,丁酸盐水平降低在帕金森病的发病和进展中起关键作用。此外,已经证明,通过益生菌、益生元、丁酸钠补充和粪便移植等方法恢复帕金森病患者的丁酸盐水平,可对该疾病的运动和非运动结局产生有益影响。本综述概述了帕金森病患者肠道细菌组成改变和相应代谢产物产生的证据,特别关注短链脂肪酸丁酸盐。除了介绍临床和临床前报告中关于短链脂肪酸的当前研究外,还讨论了在治疗背景下使用基于微生物组的方法靶向丁酸盐产生可能性的证据。