Gut Microbiome rewiring via fecal transplants: Uncovering therapeutic avenues in Alzheimer's disease models.

IF 2.3 4区 医学 Q3 NEUROSCIENCES BMC Neuroscience Pub Date : 2025-07-04 DOI:10.1186/s12868-025-00953-9
Prabhat Upadhyay, Sudhir Kumar, Anurag Tyagi, Aayush Raj Tyagi, Tarun Barbhuyan, Sarika Gupta
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Abstract

Background: Emerging evidence implicates the gut microbiome in Alzheimer's disease (AD) pathogenesis, yet the underlying mechanisms remain elusive. This study elucidates the bidirectional relationship between gut microbiota and AD using fecal microbiota transplantation (FMT) in a mouse model.

Result: Through meticulous experimentation, we conducted reciprocal FMT between AD (5xFAD) and healthy (C57BL/6) mice to unravel the impact of gut microbiome alterations on cognitive function and neuroinflammation. FMT from 5xFAD to C57BL/6 mice induced profound memory impairment and cognitive deficits, accompanied by elevated inflammatory cytokine levels, oxidative stress markers, and systemic inflammation, as evidenced by increased plasma cytokines. Conversely, transplanting healthy microbiota into 5xFAD mice yielded remarkable behavioral improvements, including enhanced spatial memory performance in the Morris water maze, directly correlating with cognitive recovery. Our findings underscore the pivotal role of the gut microbiome in AD pathogenesis and offer a promising therapeutic avenue.

Conclusion: Targeted modulation of the gut microbiome through strategies like FMT may offer potential benefits in Alzheimer's disease by influencing neuroinflammation, oxidative stress, and cognitive function. This comprehensive study provides novel insights into the gut-brain axis dynamics and paves the way for innovative microbiome-based interventions in AD management.

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肠道微生物组通过粪便移植重新布线:揭示阿尔茨海默病模型的治疗途径。
背景:越来越多的证据表明,肠道微生物群与阿尔茨海默病(AD)的发病机制有关,但其潜在机制尚不明确。本研究利用粪便微生物群移植(FMT)在小鼠模型中阐明了肠道微生物群与AD之间的双向关系。结果:通过细致的实验,我们在AD (5xFAD)和健康(C57BL/6)小鼠之间进行了互惠FMT,以揭示肠道微生物组改变对认知功能和神经炎症的影响。从5xFAD到C57BL/6小鼠的FMT诱导了深度记忆障碍和认知缺陷,伴随着炎症细胞因子水平升高,氧化应激标志物和全身炎症,血浆细胞因子增加。相反,将健康微生物群移植到5xFAD小鼠体内会产生显著的行为改善,包括莫里斯水迷宫中的空间记忆表现增强,这与认知恢复直接相关。我们的发现强调了肠道微生物组在阿尔茨海默病发病机制中的关键作用,并提供了一个有希望的治疗途径。结论:通过FMT等策略靶向调节肠道微生物组可能通过影响神经炎症、氧化应激和认知功能为阿尔茨海默病提供潜在益处。这项全面的研究为肠-脑轴动力学提供了新的见解,并为AD管理中基于微生物组的创新干预铺平了道路。
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来源期刊
BMC Neuroscience
BMC Neuroscience 医学-神经科学
CiteScore
3.90
自引率
0.00%
发文量
64
审稿时长
16 months
期刊介绍: BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.
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