Min Hou1, Gaolian Xu2, Maosheng Ran3, Wei Luo4, Hui Wang1,5. 1. School of Public Health, College of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Nano Biomedical Research Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. 3. Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, China. 4. Xinjin No. 2 People's Hospital, Chengdu, China. 5. Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: Alternations 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. OBJECTIVE: We aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD. METHODS: We 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. RESULTS: Apolipoprotein 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. CONCLUSION: The 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.
BACKGROUND: Alternations 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. OBJECTIVE: We aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD. METHODS: We 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. RESULTS: Apolipoprotein 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. CONCLUSION: The 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.
Authors: Marcus M Unger; Jörg Spiegel; Klaus-Ulrich Dillmann; David Grundmann; Hannah Philippeit; Jan Bürmann; Klaus Faßbender; Andreas Schwiertz; Karl-Herbert Schäfer Journal: Parkinsonism Relat Disord Date: 2016-08-26 Impact factor: 4.891
Authors: Floris Imhann; Arnau Vich Vila; Marc Jan Bonder; Jingyuan Fu; Dirk Gevers; Marijn C Visschedijk; Lieke M Spekhorst; Rudi Alberts; Lude Franke; Hendrik M van Dullemen; Rinze W F Ter Steege; Curtis Huttenhower; Gerard Dijkstra; Ramnik J Xavier; Eleonora A M Festen; Cisca Wijmenga; Alexandra Zhernakova; Rinse K Weersma Journal: Gut Date: 2016-10-08 Impact factor: 23.059
Authors: Colin L Masters; Randall Bateman; Kaj Blennow; Christopher C Rowe; Reisa A Sperling; Jeffrey L Cummings Journal: Nat Rev Dis Primers Date: 2015-10-15 Impact factor: 52.329
Authors: Hugues Aschard; Vincent Laville; Eric Tchetgen Tchetgen; Dan Knights; Floris Imhann; Philippe Seksik; Noah Zaitlen; Mark S Silverberg; Jacques Cosnes; Rinse K Weersma; Ramnik Xavier; Laurent Beaugerie; David Skurnik; Harry Sokol Journal: PLoS Genet Date: 2019-03-08 Impact factor: 5.917