Endres Kristina
Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Curr Alzheimer Res. 2019;16(5):405-417. doi: 10.2174/1567205016666190321163705.
There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer's disease. However, how these commensals influence disease risk and progression still has to be deciphered.
The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer's disease and are used in initial therapeutic intervention studies.
A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism in the gut, and the potential influence that the bioactive ligand may have on microbiota, gut physiology and, Alzheimer's disease.
Retinoic acid can influence neuronal functionality by means of plasticity but also by neurogenesis and modulating proteostasis. Impaired retinoid-signaling, therefore, might contribute to the development of diseases in the brain. Despite its rather direct impact, retinoic acid also influences other organ systems such as gut by regulating the residing immune cells but also factors such as permeability or commensal microbiota. These in turn can also interfere with retinoid-metabolism and via the gutbrain- axis furthermore with Alzheimer's disease pathology within the brain.
Potentially, it is yet too early to conclude from the few reports on changed microbiota in Alzheimer's disease to a dysfunctional role in retinoid-signaling. However, there are several routes how microbial commensals might affect and might be affected by vitamin A and its derivatives.
越来越多的证据表明，肠道微生物群可能在神经退行性疾病如阿尔茨海默病中发挥重要作用。然而，这些共生菌如何影响疾病风险和进展仍有待阐明。
本综述的目的是总结目前关于肠道微生物群与视黄酸之间相互作用的知识。视黄酸是重要的微量营养素之一，与阿尔茨海默病相关，且已用于初始治疗干预研究。
对文献进行选择性综述，重点关注视黄酸在健康和患病大脑中的功能、其在肠道中的代谢，以及这种生物活性配体可能对微生物群、肠道生理和阿尔茨海默病产生的潜在影响。
视黄酸可通过可塑性、神经发生和调节蛋白质稳态来影响神经元功能。因此，视黄酸信号受损可能导致脑部疾病的发生。尽管视黄酸有相当直接的影响，但它也通过调节驻留免疫细胞以及通透性或共生微生物群等因素影响肠道等其他器官系统。这些反过来也会干扰视黄酸代谢，并通过肠-脑轴进一步影响脑内的阿尔茨海默病病理。
目前，从关于阿尔茨海默病中微生物群变化的少数报告得出其在视黄酸信号传导中功能失调的结论可能还为时过早。然而，微生物共生菌可能通过多种途径影响维生素A及其衍生物，也可能受到它们的影响。
