Department of Microbiology & Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Immunol Rev. 2024 Aug;325(1):166-189. doi: 10.1111/imr.13361. Epub 2024 Jun 18.
The human gut microbiome is well-recognized as a key player in maintaining health. However, it is a dynamic entity that changes across the lifespan. How the microbial changes that occur in later decades of life shape host health or impact age-associated inflammatory neurological diseases such as multiple sclerosis (MS) is still unclear. Current understanding of the aging gut microbiome is largely limited to cross-sectional observational studies. Moreover, studies in humans are limited by confounding host-intrinsic and extrinsic factors that are not easily disentangled from aging. This review provides a comprehensive summary of existing literature on the aging gut microbiome and its known relationships with neurological diseases, with a specific focus on MS. We will also discuss preclinical animal models and human studies that shed light on the complex microbiota-host interactions that have the potential to influence disease pathology and progression in aging individuals. Lastly, we propose potential avenues of investigation to deconvolute features of an aging microbiota that contribute to disease, or alternatively promote health in advanced age.
人类肠道微生物组被认为是维持健康的关键因素。然而,它是一个动态的实体,会随着生命周期而变化。在生命的后几十年中发生的微生物变化如何塑造宿主健康或影响多发性硬化症 (MS) 等与年龄相关的炎症性神经疾病仍然不清楚。目前对衰老肠道微生物组的理解在很大程度上仅限于横断面观察性研究。此外,人类的研究受到宿主内在和外在因素的混淆的限制,这些因素不容易从衰老中分离出来。本综述全面总结了关于衰老肠道微生物组及其与神经疾病(特别是多发性硬化症)已知关系的现有文献。我们还将讨论临床前动物模型和人类研究,这些研究揭示了复杂的微生物-宿主相互作用,这些相互作用有可能影响衰老个体的疾病病理和进展。最后,我们提出了一些潜在的研究途径,可以剖析导致疾病的衰老微生物组的特征,或者在老年时促进健康。