Gut Microbiota Mediates Neuroinflammation in Alzheimer’s Disease: Unraveling Key Factors and Mechanistic Insights

Junyi, Liang; Yueyang, Wang; Bin, Liu; Xiaohong, Dong; Wenhui, Cai; Ning, Zhang; Hong, Zhang

doi:10.1007/s12035-024-04513-w

Mol Neurobiol

2024

DOI: 10.1007/s12035-024-04513-w

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Gut Microbiota Mediates Neuroinflammation in Alzheimer’s Disease: Unraveling Key Factors and Mechanistic Insights

Liang Junyi,

Wang Yueyang,

Liu Bin

et al.

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2024

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Cited by 2 publications

References 204 publications

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Gut microbiota in health and disease: advances and future prospects

Zhang,

Wang,

Sang

et al. 2024

MedComm

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The gut microbiota plays a critical role in maintaining human health, influencing a wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances in gut microbiota composition can contribute to the onset and progression of various diseases, such as metabolic disorders (e.g., obesity and diabetes) and neurodegenerative conditions (e.g., Alzheimer's and Parkinson's). These conditions are often accompanied by chronic inflammation and dysregulated immune responses, which are closely linked to specific forms of cell death, including pyroptosis and ferroptosis. Pathogenic bacteria in the gut can trigger these cell death pathways through toxin release, while probiotics have been found to mitigate these effects by modulating immune responses. Despite these insights, the precise mechanisms through which the gut microbiota influences these diseases remain insufficiently understood. This review consolidates recent findings on the impact of gut microbiota in these immune‐mediated and inflammation‐associated conditions. It also identifies gaps in current research and explores the potential of advanced technologies, such as organ‐on‐chip models and the microbiome–gut–organ axis, for deepening our understanding. Emerging tools, including single‐bacterium omics and spatial metabolomics, are discussed for their promise in elucidating the microbiota's role in disease development.

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Gut microbiota in health and disease: advances and future prospects

Zhang,

Wang,

Sang

et al. 2024

MedComm

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Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement

Popescu,

Munteanu,

Anghelescu

et al. 2024

IJMS

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Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota–gut–brain axis, including in Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients’ gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.

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Gut Microbiota Mediates Neuroinflammation in Alzheimer’s Disease: Unraveling Key Factors and Mechanistic Insights

Cited by 2 publications

References 204 publications

Gut microbiota in health and disease: advances and future prospects

Gut microbiota in health and disease: advances and future prospects

Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement

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