Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
J Intern Med. 2021 Oct;290(4):758-788. doi: 10.1111/joim.13336. Epub 2021 Jul 8.
Amyotrophic lateral sclerosis (ALS), characterized by a loss of motor neurons in the brain and spinal cord, is a relatively rare but currently incurable neurodegenerative disease. The global incidence of ALS is estimated as 1.75 per 100,000 person-years and the global prevalence is estimated as 4.1-8.4 per 100,000 individuals. Contributions from outside the central nervous system to the etiology of ALS have been increasingly recognized. Gut microbiome is one of the most quickly growing fields of research for ALS. In this article, we performed a comprehensive review of the results from existing animal and human studies, to provide an up-to-date summary of the current research on gut microbiome and ALS. In brief, we found relatively consistent results from animal studies, suggesting an altered gut microbiome composition in experimental ALS. Publication bias might however be a concern. Findings from human studies are largely inconclusive. A few animal and human studies demonstrated the usefulness of intervention with microbial-derived metabolites in modulating the disease progression of ALS. We discussed potential methodological concerns in these studies, including study design, statistical power, handling process of biospecimens and sequencing data, as well as statistical methods and interpretation of results. Finally, we made a few proposals for continued microbiome research in ALS, with the aim to provide valid, reproducible, and translatable findings.
肌萎缩侧索硬化症（ALS），特征是大脑和脊髓中的运动神经元丧失，是一种相对罕见但目前无法治愈的神经退行性疾病。全球 ALS 的发病率估计为每 10 万人年 1.75 例，全球患病率估计为每 10 万人 4.1-8.4 例。越来越多的人认识到，中枢神经系统以外的因素对 ALS 的病因有贡献。肠道微生物组是 ALS 研究中发展最快的领域之一。在本文中，我们对现有的动物和人类研究结果进行了全面回顾，为肠道微生物组与 ALS 的当前研究提供了最新的总结。简而言之，我们从动物研究中发现了相对一致的结果，表明实验性 ALS 中肠道微生物组组成发生了改变。然而，可能存在发表偏倚的问题。人类研究的结果基本上没有定论。少数动物和人类研究表明，微生物衍生代谢物的干预在调节 ALS 的疾病进展方面具有一定作用。我们讨论了这些研究中潜在的方法学问题，包括研究设计、统计能力、生物样本和测序数据的处理过程，以及统计方法和结果解释。最后，我们对 ALS 中的微生物组研究提出了一些建议，旨在提供有效、可重复和可转化的发现。
