University of Texas Medical Branch, Department of Neurology, Galveston, TX, United States of America.
University of Texas at San Antonio, Department of Biology, San Antonio, TX, United States of America.
Neurobiol Dis. 2021 Aug;156:105403. doi: 10.1016/j.nbd.2021.105403. Epub 2021 Jun 1.
Sporadic late-onset Alzheimer's disease (AD) is the most frequent cause of dementia associated with aging. Due to the progressive aging of the population, AD is becoming a healthcare burden of unprecedented proportions. Twenty years ago, it was reported that some indole molecules produced by the gut microbiota possess essential biological activities, including neuroprotection and antioxidant properties. Since then, research has cemented additional characteristics of these substances, including anti-inflammatory, immunoregulatory, and amyloid anti-aggregation features. Herein, we summarize the evidence supporting an integrated hypothesis that some of these substances can influence the age of onset and progression of AD and are central to the symbiotic relationship between intestinal microbes and the brain. Studies have shown that some of these substances' activities result from interactions with biologically conserved pathways and with genetic risk factors for AD. By targeting multiple pathologic mechanisms simultaneously, certain indoles may be excellent candidates to ameliorate neurodegeneration. We propose that management of the microbiota to induce a higher production of neuroprotective indoles (e.g., indole propionic acid) will promote brain health during aging. This area of research represents a new therapeutic paradigm that could add functional years of life to individuals who would otherwise develop dementia.
散发性迟发性阿尔茨海默病 (AD) 是与衰老相关的痴呆症最常见的病因。由于人口的老龄化进程不断推进，AD 正在成为前所未有的医疗保健负担。二十年前，有报道称肠道微生物群产生的一些吲哚分子具有重要的生物学活性，包括神经保护和抗氧化特性。从那时起，研究进一步证实了这些物质的其他特性，包括抗炎、免疫调节和抗淀粉样蛋白聚集特性。在此，我们总结了支持以下综合假说的证据，即其中一些物质可以影响 AD 的发病年龄和进展，并与肠道微生物和大脑的共生关系密切相关。研究表明，这些物质的某些活性源自与生物保守途径和 AD 的遗传风险因素的相互作用。某些吲哚类化合物通过同时针对多种病理机制，可能是改善神经退行性变的理想候选药物。我们提出，通过管理微生物群来诱导产生更多的神经保护吲哚（如吲哚丙酸），将促进老年人的大脑健康。这一研究领域代表了一种新的治疗范例，可以为那些否则会发展为痴呆症的人增加健康寿命。
