Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, 05508000, SP, Brazil.
Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, 05508080, SP, Brazil.
Metab Brain Dis. 2024 Jun;39(5):967-984. doi: 10.1007/s11011-024-01369-w. Epub 2024 Jun 7.
The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota.
人口老龄化是一种全球现象,随着神经退行性疾病发病率的增加,这种现象可能会加剧。阿尔茨海默病、帕金森病、多发性硬化症、肌萎缩侧索硬化症和亨廷顿病等神经退行性疾病是老龄化可能引发或加重的疾病。最近的研究表明,肠道微生物群落失调可能会引发代谢和大脑功能障碍,从而导致这些神经退行性疾病的病因和发病机制。肠道微生物群落及其代谢物在免疫系统调节(发育和成熟)、维持肠道屏障完整性、调节肠道神经肌肉功能以及促进微生物和人类的基本代谢过程等方面具有重要作用。支持肠道微生物群落及其代谢物与神经退行性疾病之间联系的主要证据是流行病学观察和动物模型实验。本文综述了肠道微生物群-肠-脑轴与神经退行性疾病之间的最新关联证据,特别关注肠道代谢物。肠道微生物群落失调会增加炎症细胞因子和细菌代谢物,改变肠道和血脑屏障通透性,引发神经炎症,从而促进神经退行性疾病的发病机制。支持这一证据的临床数据仍需改善。大多数发现的研究都是描述性的,与神经退行性疾病中存在的细菌门或物种有关。尽管最近的研究存在局限性,但通过研究宿主和微生物群落之间的相互作用,有可能阐明目前在健康和疾病的流行病理生理学框架中尚未阐明的临床问题。