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Apolipoprotein E genotype‐dependent nutrigenetic effects to prebiotic inulin for reducing risk for Alzheimer’s disease in a mouse model
Author(s) -
Chang YaHsuan,
Hoffman Jared D,
Yanckello Lucille M,
McCulloch Scott D,
Lin Penghui,
Lane Andrew N,
Chlipala George,
Green Stefan J,
Lin AiLing
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041175
Subject(s) - inulin , prebiotic , biology , apolipoprotein e , endocrinology , genotype , medicine , biochemistry , disease , gene
Background Apolipoprotein E ε4 ( APOE4 ) allele is the strongest genetic risk factor for Alzheimer’s disease (AD). Cognitively normal APOE4 carriers show an early decline in brain metabolic functions and gut microbiome dysbiosis before the onset of AD compared to APOE3 carriers. Our laboratory previously found that inulin, a prebiotic, is effective to restore metabolic functions and gut microbiome balance, and thus reduce risk for AD in an ApoE4 mouse model (Hoffman et al., 2019). However, whether the responses to the inulin diet are APOE allele‐dependent remains unknown. Therefore, our objective was to identify whether inulin would differently contribute to metabolic and gut microbiome changes due to APOE genotype. Method We fed 3‐month‐old asymptomatic ApoE3 ( E3 FAD) and ApoE4 ( E4 FAD) mice a prebiotic inulin diet or a control diet containing cellulose for 4 months (N=15/group; Male:Female=1:1). After 4 months, we used magnetic resonance spectroscopy to measure in vivo brain scyllo‐inositol level, a compound that has been demonstrated to inhibit amyloid β aggregation (Fenili, Brown, Rappaport, & McLaurin, 2007). We collected the fecal samples for gut microbiome sequencing, and cecal and blood samples for metabolomic profiling. Result Inulin induced scyllo‐inositol in hippocampus of the brain with a higher level in E4 FAD mice. Inulin increased blood metabolites in tryptophan and tyrosine metabolic pathways that enhance nervous system in E3 FAD mice. It increased blood metabolites in pentose phosphate pathway and citric acid cycle that support nucleotides and nucleic acids biosynthesis and energy production in E4 FAD mice. These alterations in hippocampus and blood showed inulin’s impacts on systemic metabolism depending on mouse ApoE genotypes. Inulin enhanced short chain fatty acids in cecum with a greater increase in E3 FAD mice. E3 FAD mice showed more distinct gut microbiome patterns between inulin and control groups compared to E4 FAD mice. Conclusion Inulin‐induced systemic metabolism and gut microbiome changes are APOE genotype‐dependent. Our study contributes to the gut‐brain axis research and potential AD prevention. Future studies can design human interventions that facilitate the guide of personalized nutrition in APOE3 and APOE4 population to prevent AD.