APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease
BackgroundAlternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.ObjectiveWe aimed to explore associations of the risk gen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.619051/full |
| _version_ | 1818416201916743680 |
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| author | Min Hou Gaolian Xu Maosheng Ran Wei Luo Hui Wang Hui Wang |
| author_facet | Min Hou Gaolian Xu Maosheng Ran Wei Luo Hui Wang Hui Wang |
| author_sort | Min Hou |
| collection | DOAJ |
| description | BackgroundAlternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.ObjectiveWe aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD.MethodsWe collected baseline data and stool and blood samples from 30 AD patients and 47 healthy controls in a case-control study. The rs42358/rs4512 (ApoE), rs3851179 (PICALM), rs744373 (BIN1), rs9331888 (CLU), rs670139 (MS4A4E), rs3764650 (ABCA7), rs3865444 (CD33), rs9349407 (CD2AP), rs11771145 (EPHA1), and rs3818361/rs6656401 (CR1) were sequenced, and microbiota composition was characterized using 16S rRNA gene sequencing. The associations of the altered gut bacteria with the risk genetics were analyzed.ResultsApolipoprotein ε4 allele and rs744373 were risk loci for the AD among 12 genetic variants. Phylum Proteobacteria; orders Enterobacteriales, Deltaproteobacteria, and Desulfovibrionales; families Enterobacteriaceae and Desulfovibrionaceae; and genera Escherichia–Shigella, Ruminococcaceae_UCG_002, Shuttleworthia, Anaerofustis, Morganelia, Finegoldia, and Anaerotruncus were increased in AD subjects, whereas family Enterococcaceae and genera Megamonas, Enterococcus, and Anaerostipes were more abundant in controls (P < 0.05). Among the altered microbiota, APOE ε4 allele was positively associated with pathogens: Proteobacteria.ConclusionThe interaction of APOE ε4 gene and the AD-promoting pathogens might be an important factor requiring for the promotion of AD. Targeting to microbiota might be an effective therapeutic strategy for AD susceptible to APOE ε4 allele. This needs further investigation. |
| first_indexed | 2024-12-14T11:47:08Z |
| format | Article |
| id | doaj.art-626a952b5dad4fc294def247e40f2b80 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T11:47:08Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-626a952b5dad4fc294def247e40f2b802022-12-21T23:02:32ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-02-011510.3389/fnins.2021.619051619051APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer DiseaseMin Hou0Gaolian Xu1Maosheng Ran2Wei Luo3Hui Wang4Hui Wang5School of Public Health, College of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaNano Biomedical Research Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Social Work and Social Administration, The University of Hong Kong, Hong Kong, ChinaXinjin No. 2 People’s Hospital, Chengdu, ChinaSchool of Public Health, College of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaCenter for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundAlternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.ObjectiveWe aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD.MethodsWe collected baseline data and stool and blood samples from 30 AD patients and 47 healthy controls in a case-control study. The rs42358/rs4512 (ApoE), rs3851179 (PICALM), rs744373 (BIN1), rs9331888 (CLU), rs670139 (MS4A4E), rs3764650 (ABCA7), rs3865444 (CD33), rs9349407 (CD2AP), rs11771145 (EPHA1), and rs3818361/rs6656401 (CR1) were sequenced, and microbiota composition was characterized using 16S rRNA gene sequencing. The associations of the altered gut bacteria with the risk genetics were analyzed.ResultsApolipoprotein ε4 allele and rs744373 were risk loci for the AD among 12 genetic variants. Phylum Proteobacteria; orders Enterobacteriales, Deltaproteobacteria, and Desulfovibrionales; families Enterobacteriaceae and Desulfovibrionaceae; and genera Escherichia–Shigella, Ruminococcaceae_UCG_002, Shuttleworthia, Anaerofustis, Morganelia, Finegoldia, and Anaerotruncus were increased in AD subjects, whereas family Enterococcaceae and genera Megamonas, Enterococcus, and Anaerostipes were more abundant in controls (P < 0.05). Among the altered microbiota, APOE ε4 allele was positively associated with pathogens: Proteobacteria.ConclusionThe interaction of APOE ε4 gene and the AD-promoting pathogens might be an important factor requiring for the promotion of AD. Targeting to microbiota might be an effective therapeutic strategy for AD susceptible to APOE ε4 allele. This needs further investigation.https://www.frontiersin.org/articles/10.3389/fnins.2021.619051/fullAlzheimer diseaseapolipoprotein Edysbiosisgenetic variantsgut microbiome |
| spellingShingle | Min Hou Gaolian Xu Maosheng Ran Wei Luo Hui Wang Hui Wang APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease Frontiers in Neuroscience Alzheimer disease apolipoprotein E dysbiosis genetic variants gut microbiome |
| title | APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease |
| title_full | APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease |
| title_fullStr | APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease |
| title_full_unstemmed | APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease |
| title_short | APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease |
| title_sort | apoe ε4 carrier status and gut microbiota dysbiosis in patients with alzheimer disease |
| topic | Alzheimer disease apolipoprotein E dysbiosis genetic variants gut microbiome |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.619051/full |
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