Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation
Abstract Alzheimer’s disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to p...
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BMC
2025-01-01
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| Series: | Behavioral and Brain Functions |
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| Online Access: | https://doi.org/10.1186/s12993-024-00265-8 |
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| author | Xiang Li Qingyong Ding Xinxin Wan Qilong Wu Shiqing Ye Yongliang Lou |
| author_facet | Xiang Li Qingyong Ding Xinxin Wan Qilong Wu Shiqing Ye Yongliang Lou |
| author_sort | Xiang Li |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice. |
| format | Article |
| id | doaj-art-cc29dd8c422b45129eefd3e6f25f27dc |
| institution | Kabale University |
| issn | 1744-9081 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Behavioral and Brain Functions |
| spelling | doaj-art-cc29dd8c422b45129eefd3e6f25f27dc2025-01-12T12:33:12ZengBMCBehavioral and Brain Functions1744-90812025-01-0121112110.1186/s12993-024-00265-8Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammationXiang Li0Qingyong Ding1Xinxin Wan2Qilong Wu3Shiqing Ye4Yongliang Lou5Wenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical UniversityAbstract Alzheimer’s disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.https://doi.org/10.1186/s12993-024-00265-8Alzheimer’s diseaseInflammationFecal microbiota transplantationIntestinal microbiotaShort-chain fatty acidsMicrobiota-gut-brain axis |
| spellingShingle | Xiang Li Qingyong Ding Xinxin Wan Qilong Wu Shiqing Ye Yongliang Lou Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation Behavioral and Brain Functions Alzheimer’s disease Inflammation Fecal microbiota transplantation Intestinal microbiota Short-chain fatty acids Microbiota-gut-brain axis |
| title | Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation |
| title_full | Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation |
| title_fullStr | Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation |
| title_full_unstemmed | Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation |
| title_short | Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation |
| title_sort | fecal microbiota transplantation attenuates alzheimer s disease symptoms in app ps1 transgenic mice via inhibition of the tlr4 myd88 nf κb signaling pathway mediated inflammation |
| topic | Alzheimer’s disease Inflammation Fecal microbiota transplantation Intestinal microbiota Short-chain fatty acids Microbiota-gut-brain axis |
| url | https://doi.org/10.1186/s12993-024-00265-8 |
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