Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau hyperphosphorylation, and chronic neuroinflammation. While neuroinflammation—mediated by microglial and astrocyte activation—has long been considered a secondary response to Aβ pathol...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1582119/full |
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| author | Wenhui Lei Wenhui Lei Yiwen Cheng Xia Liu Jie Gao Zhangcheng Zhu Wenwen Ding Wenwen Ding Xiaocui Xu Xiaocui Xu Yating Li Zongxin Ling Ruilai Jiang Xiaoying Chen |
| author_facet | Wenhui Lei Wenhui Lei Yiwen Cheng Xia Liu Jie Gao Zhangcheng Zhu Wenwen Ding Wenwen Ding Xiaocui Xu Xiaocui Xu Yating Li Zongxin Ling Ruilai Jiang Xiaoying Chen |
| author_sort | Wenhui Lei |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau hyperphosphorylation, and chronic neuroinflammation. While neuroinflammation—mediated by microglial and astrocyte activation—has long been considered a secondary response to Aβ pathology, emerging evidence positions it as a primary driver of cognitive decline. Notably, the gut microbiota, through the microbiota-gut-brain axis (MGBA), is crucial in modulating neuroinflammation. Dysbiosis disrupts gut barrier integrity, promotes systemic inflammation, and exacerbates neuroinflammatory responses, thereby accelerating AD progression. Recent advances reveal that gut microbiota-derived metabolites (e.g., short-chain fatty acids, lipopolysaccharides) directly influence microglial activation and Aβ aggregation. These findings have opened new therapeutic possibilities, with microbiota-targeted approaches such as probiotics, prebiotics, and fecal microbiota transplantation demonstrating promising neuroprotective effects in preclinical studies by reducing neuroinflammation and preserving cognitive function. However, translating these findings into clinical applications requires further validation through randomized controlled trials. This review summarizes the current understanding of gut microbiota-driven neuroinflammation in AD, from molecular mechanisms to potential therapeutic strategies. Targeting the MGBA represents a paradigm shift in AD management, emphasizing the modulation of neuroinflammation and pathological progression through gut microbiota interventions. The discussion also addresses existing research challenges and outlines future directions to advance this promising field. |
| format | Article |
| id | doaj-art-b1cd7300356e4af0acd04efb106fd482 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b1cd7300356e4af0acd04efb106fd4822025-08-20T03:32:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15821191582119Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunitiesWenhui Lei0Wenhui Lei1Yiwen Cheng2Xia Liu3Jie Gao4Zhangcheng Zhu5Wenwen Ding6Wenwen Ding7Xiaocui Xu8Xiaocui Xu9Yating Li10Zongxin Ling11Ruilai Jiang12Xiaoying Chen13Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaJinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, ChinaMedical School of Nantong University, Nantong, Jiangsu, ChinaDepartment of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, ChinaMedical School of Nantong University, Nantong, Jiangsu, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Intensive Care Unit, Lishui Second People’s Hospital, Lishui, Zhejiang, ChinaDepartment of Intensive Care Unit, Lishui Second People’s Hospital, Lishui, Zhejiang, ChinaAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau hyperphosphorylation, and chronic neuroinflammation. While neuroinflammation—mediated by microglial and astrocyte activation—has long been considered a secondary response to Aβ pathology, emerging evidence positions it as a primary driver of cognitive decline. Notably, the gut microbiota, through the microbiota-gut-brain axis (MGBA), is crucial in modulating neuroinflammation. Dysbiosis disrupts gut barrier integrity, promotes systemic inflammation, and exacerbates neuroinflammatory responses, thereby accelerating AD progression. Recent advances reveal that gut microbiota-derived metabolites (e.g., short-chain fatty acids, lipopolysaccharides) directly influence microglial activation and Aβ aggregation. These findings have opened new therapeutic possibilities, with microbiota-targeted approaches such as probiotics, prebiotics, and fecal microbiota transplantation demonstrating promising neuroprotective effects in preclinical studies by reducing neuroinflammation and preserving cognitive function. However, translating these findings into clinical applications requires further validation through randomized controlled trials. This review summarizes the current understanding of gut microbiota-driven neuroinflammation in AD, from molecular mechanisms to potential therapeutic strategies. Targeting the MGBA represents a paradigm shift in AD management, emphasizing the modulation of neuroinflammation and pathological progression through gut microbiota interventions. The discussion also addresses existing research challenges and outlines future directions to advance this promising field.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1582119/fullAlzheimer’s diseasebutyratefecal microbiota transplantationneuroinflammationgut microbiotamicrobiota-gut-brain axis |
| spellingShingle | Wenhui Lei Wenhui Lei Yiwen Cheng Xia Liu Jie Gao Zhangcheng Zhu Wenwen Ding Wenwen Ding Xiaocui Xu Xiaocui Xu Yating Li Zongxin Ling Ruilai Jiang Xiaoying Chen Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities Frontiers in Immunology Alzheimer’s disease butyrate fecal microbiota transplantation neuroinflammation gut microbiota microbiota-gut-brain axis |
| title | Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities |
| title_full | Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities |
| title_fullStr | Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities |
| title_full_unstemmed | Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities |
| title_short | Gut microbiota-driven neuroinflammation in Alzheimer’s disease: from mechanisms to therapeutic opportunities |
| title_sort | gut microbiota driven neuroinflammation in alzheimer s disease from mechanisms to therapeutic opportunities |
| topic | Alzheimer’s disease butyrate fecal microbiota transplantation neuroinflammation gut microbiota microbiota-gut-brain axis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1582119/full |
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