肠道微生物群与微小RNA相互作用的综述:对阿尔茨海默病的影响

A review on gut microbiota and miRNA crosstalk: implications for Alzheimer's disease.

作者信息

Ayyanar Maruthu Pandian, Vijayan Murali

机构信息

Department of Biology, The Gandhigram Rural Institute (Deemed to be University), Gandhigram, 624302, Tamil Nadu, India.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.

出版信息

Geroscience. 2025 Feb;47(1):339-385. doi: 10.1007/s11357-024-01432-5. Epub 2024 Nov 19.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,其特征为认知功能衰退和神经元进行性损伤。最近的研究突显了肠道微生物群和微小RNA(miRNA)在AD发病机制中的重要作用。本综述探讨了肠道微生物群与miRNA之间的复杂相互作用,强调了它们对阿尔茨海默病进展的综合影响。首先,我们讨论肠-脑轴内的双向通信,以及肠道菌群失调如何导致AD中的神经炎症和神经退行性变。阿尔茨海默病患者肠道微生物群组成的变化与炎症有关,炎症会加剧疾病进展。接下来,我们深入研究miRNA的生物学特性,重点关注它们在基因调控、神经发育和神经退行性变中的作用。miRNA失调与AD发病机制有关,影响炎症、tau病理和淀粉样蛋白沉积等关键过程。然后,我们研究肠道微生物群如何调节miRNA表达,特别是在大脑中,这可能会改变神经炎症反应和突触可塑性。肠道微生物群与miRNA之间的相互作用还会影响血脑屏障的完整性,进一步促使阿尔茨海默病病理变化的发生。最后,我们探索针对这种肠道微生物群-miRNA轴的治疗策略,包括益生菌、益生元及饮食干预,旨在调节miRNA表达并改善AD的治疗效果。尽管前景广阔,但在充分阐明这些相互作用并将其转化为有效疗法方面仍存在挑战。本综述强调了了解AD中肠道微生物群与miRNA关系的重要性,为旨在减缓疾病进展的新型治疗方法提供了潜在途径。

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