The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer's Disease.
The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer's Disease.
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三重联盟：与年龄相关的认知衰退和阿尔茨海默氏病背景下的微生物组、线粒体和代谢物。
DOI：
10.1093/gerona/glad226
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Yadav,Hariom
中科院分区：
文献类型：
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作者：
Prajapati,SantoshK;Shah,Ria;Alford,Nicholas;Mishra,SidharthP;Jain,Shalini;Hansen,Barbara;Sanberg,Paul;Molina,AnthonyJA;Yadav,Hariom
阿尔茨海默病（AD）是一种进行性的、与年龄相关的神经退行性疾病，影响大部分老年人。它目前缺乏有效的治疗方法，给患者、家庭、医疗保健系统和社会带来了沉重的负担。这主要是由于我们对AD进展的病理生理学的理解有限，以及缺乏有效的药物靶点和干预时机来解决潜在的病理学。AD是一种多因素疾病，新出现的证据表明，肠道微生物群的异常作为AD的环境和多方面贡献者发挥着重要作用，尽管确切的机制尚未完全探索。微生物群组成的变化通过其代谢物影响宿主神经元健康。这些代谢物通过影响线粒体功能调节肠上皮细胞、血脑屏障通透性和神经炎症。在衰老和AD期间，有益微生物及其必需代谢产物的比例下降与线粒体功能低下直接相关，尽管具体机制尚不清楚。在这篇综述中，我们讨论了了解微生物组及其代谢产物对各种细胞类型的影响，它们对肠道和血脑屏障完整性的影响，全身和脑炎症以及AD病理学中细胞特异性效应的最新进展。这些信息有望为AD中微生物群和线粒体之间的相互作用的新理解铺平道路，为开发AD的新治疗方法提供基础。
Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored. Changes in the composition of microbiota influence host neuronal health through their metabolites. These metabolites regulate intestinal epithelia, blood-brain barrier permeability, and neuroinflammation by affecting mitochondrial function. The decline in the proportion of beneficial microbes and their essential metabolites during aging and AD is directly linked to poor mitochondrial function, although the specific mechanisms remain unclear. In this review, we discuss recent developments in understanding the impact of the microbiome and its metabolites on various cell types, their influence on the integrity of the gut and blood-brain barriers, systemic and brain inflammation, and cell-specific effects in AD pathology. This information is expected to pave the way for a new understanding of the interactions between microbiota and mitochondria in AD, providing a foundation for the development of novel treatments for AD.