Tan Ai Huey, Hor Jia Wei, Chong Chun Wie, Lim Shen-Yang
Division of Neurology and the Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, Faculty of Medicine University of Malaya Kuala Lumpur Malaysia.
School of Pharmacy Monash University Malaysia Selangor Malaysia.
JGH Open. 2020 Nov 20;5(4):414-419. doi: 10.1002/jgh3.12450. eCollection 2021 Apr.
The gut-brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short-chain fatty acids in PD. In this regard, microbial-directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/"normalization" of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo-controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long-term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.
肠-脑轴是帕金森病(PD)研究中的一个热门话题。据推测,肠道病原体和生态失调可能导致外周炎症状态,或引发下游代谢效应,从而加剧PD的神经退行性病变过程。多项临床前和临床研究表明,PD患者存在肠道通透性破坏、肠道炎症、肠道微生物群改变以及粪便短链脂肪酸减少等情况。在这方面,益生菌等微生物导向疗法正成为潜在的治疗选择。由于这些活微生物具有多种功能,包括抑制病原体定植、调节/“正常化”微生物群及其功能、免疫调节作用(如减轻炎症)以及改善宿主上皮屏障功能,因此补充益生菌被认为具有多种健康益处。有趣的是,多项PD动物模型研究表明,益生菌在减少多巴胺能神经元变性方面具有潜在的神经保护作用。值得注意的是,两项随机安慰剂对照试验为益生菌治疗PD便秘提供了I类证据。然而,益生菌对PD其他方面(如运动功能障碍和认知功能)的影响及其长期疗效(包括对肠道中PD药物吸收的影响)尚未得到充分研究。还需要进一步开展有针对性的动物和人体研究,以了解益生菌在PD中的作用机制,并根据个体宿主情况调整益生菌疗法,从而改善这种致残性疾病患者的治疗效果。