Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43
Abstract Background Alzheimer’s disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal mi...
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BMC
2025-01-01
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| Series: | Microbiome |
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| Online Access: | https://doi.org/10.1186/s40168-024-02001-w |
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| author | Zifan Wang Cai Wang Boyu Yuan Li Liu Haoming Zhang Mingqiang Zhu Hongxia Chai Jie Peng Yanhua Huang Shuo Zhou Juxiong Liu Liyong Wu Wei Wang |
| author_facet | Zifan Wang Cai Wang Boyu Yuan Li Liu Haoming Zhang Mingqiang Zhu Hongxia Chai Jie Peng Yanhua Huang Shuo Zhou Juxiong Liu Liyong Wu Wei Wang |
| author_sort | Zifan Wang |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal microbiota metabolism have been considered to be important factors affecting central nervous system (CNS) homeostasis. Among the main mediators of host-microbe interactions, volatile fatty acids play a crucial role. Nevertheless, the influence and pathways of microorganisms and their metabolites on Alzheimer’s disease (AD) remain uncertain. Results In this study, we present distinctions in blood and fecal SCFA levels and microbiota composition between healthy individuals and those diagnosed with AD. We found that AD patients showed a decrease in the abundance of Akkermansia muciniphila and a decrease in propionic acid both in fecal and in blood. In order to further reveal the effects and the mechanisms of propionic acid on AD prevention, we systematically explored the effects of propionic acid administration on AD model mice and cultured hippocampal neuronal cells. Results showed that oral propionate supplementation ameliorated cognitive impairment in AD mice. Propionate downregulated mitochondrial fission protein (DRP1) via G-protein coupled receptor 41 (GPR41) and enhanced PINK1/PARKIN-mediated mitophagy via G-protein coupled receptor 43 (GPR43) in AD pathophysiology which contribute to maintaining mitochondrial homeostasis both in vivo and in vitro. Administered A. muciniphila to AD mice before disease onset showed improved cognition, mitochondrial division and mitophagy in AD mice. Conclusions Taken together, our results demonstrate that A. muciniphila and its metabolite propionate protect against AD-like pathological events in AD mouse models by targeting mitochondrial homeostasis, making them promising therapeutic candidates for the prevention and treatment of AD. Video Abstract |
| format | Article |
| id | doaj-art-5cffc3cf3d5641e6bc6fe7ae2f28272e |
| institution | Kabale University |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-5cffc3cf3d5641e6bc6fe7ae2f28272e2025-01-26T12:43:11ZengBMCMicrobiome2049-26182025-01-0113112610.1186/s40168-024-02001-wAkkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43Zifan Wang0Cai Wang1Boyu Yuan2Li Liu3Haoming Zhang4Mingqiang Zhu5Hongxia Chai6Jie Peng7Yanhua Huang8Shuo Zhou9Juxiong Liu10Liyong Wu11Wei Wang12Innovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInternal Medicine Ward, Zhanlan Road Hospital, Xicheng DistrictDepartment of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Neurology, Xuanwu Hospital, Capital Medical UniversityInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceKey Laboratory of Zoonoses Research, Ministry of Education, Jilin UniversityDepartment of Neurology, Xuanwu Hospital, Capital Medical UniversityInnovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong ProvinceAbstract Background Alzheimer’s disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal microbiota metabolism have been considered to be important factors affecting central nervous system (CNS) homeostasis. Among the main mediators of host-microbe interactions, volatile fatty acids play a crucial role. Nevertheless, the influence and pathways of microorganisms and their metabolites on Alzheimer’s disease (AD) remain uncertain. Results In this study, we present distinctions in blood and fecal SCFA levels and microbiota composition between healthy individuals and those diagnosed with AD. We found that AD patients showed a decrease in the abundance of Akkermansia muciniphila and a decrease in propionic acid both in fecal and in blood. In order to further reveal the effects and the mechanisms of propionic acid on AD prevention, we systematically explored the effects of propionic acid administration on AD model mice and cultured hippocampal neuronal cells. Results showed that oral propionate supplementation ameliorated cognitive impairment in AD mice. Propionate downregulated mitochondrial fission protein (DRP1) via G-protein coupled receptor 41 (GPR41) and enhanced PINK1/PARKIN-mediated mitophagy via G-protein coupled receptor 43 (GPR43) in AD pathophysiology which contribute to maintaining mitochondrial homeostasis both in vivo and in vitro. Administered A. muciniphila to AD mice before disease onset showed improved cognition, mitochondrial division and mitophagy in AD mice. Conclusions Taken together, our results demonstrate that A. muciniphila and its metabolite propionate protect against AD-like pathological events in AD mouse models by targeting mitochondrial homeostasis, making them promising therapeutic candidates for the prevention and treatment of AD. Video Abstracthttps://doi.org/10.1186/s40168-024-02001-wPropionic acidAlzheimer’s diseaseAkkermansia muciniphilaMitochondrial division and mitophagy |
| spellingShingle | Zifan Wang Cai Wang Boyu Yuan Li Liu Haoming Zhang Mingqiang Zhu Hongxia Chai Jie Peng Yanhua Huang Shuo Zhou Juxiong Liu Liyong Wu Wei Wang Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 Microbiome Propionic acid Alzheimer’s disease Akkermansia muciniphila Mitochondrial division and mitophagy |
| title | Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 |
| title_full | Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 |
| title_fullStr | Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 |
| title_full_unstemmed | Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 |
| title_short | Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer’s disease pathologic process via GPR41 and GPR43 |
| title_sort | akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during alzheimer s disease pathologic process via gpr41 and gpr43 |
| topic | Propionic acid Alzheimer’s disease Akkermansia muciniphila Mitochondrial division and mitophagy |
| url | https://doi.org/10.1186/s40168-024-02001-w |
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