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, 7 (1), 13510

Therapeutic Potential of Bifidobacterium Breve Strain A1 for Preventing Cognitive Impairment in Alzheimer's Disease

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Therapeutic Potential of Bifidobacterium Breve Strain A1 for Preventing Cognitive Impairment in Alzheimer's Disease

Yodai Kobayashi et al. Sci Rep.

Abstract

It has previously been shown that the consumption of probiotics may have beneficial effects not only on peripheral tissues but also on the central nervous system and behavior via the microbiota-gut-brain axis, raising the possibility that treatment with probiotics could be an effective therapeutic strategy for managing neurodegenerative disorders. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on behavior and physiological processes in Alzheimer's disease (AD) model mice. We found that administration of B. breve A1 to AD mice reversed the impairment of alternation behavior in a Y maze test and the reduced latency time in a passive avoidance test, indicating that it prevented cognitive dysfunction. We also demonstrated that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitive decline observed in AD mice. Gene profiling analysis revealed that the consumption of B. breve A1 suppressed the hippocampal expressions of inflammation and immune-reactive genes that are induced by amyloid-β. Together, these findings suggest that B. breve A1 has therapeutic potential for preventing cognitive impairment in AD.

Conflict of interest statement

Authors Y.K., H.S., E.M., T.K. and J.Z.X. are the employee of Morinaga Milk Industry Co., Ltd.

Figures

Figure 1
Figure 1
Effect of Bifidobacterium breve strain A1 treatment on cognitive function in AD model mice evaluated by Y maze test and passive avoidance test. (a) Experimental design of the mouse study. An animal model of AD was induced by intracerebroventricular (ICV) injection of Aβ25–35 or Aβ1–42. The probiotics was orally administered every day starting 2 days before ICV injection. 6 days after ICV, cognitive function was evaluated by Y maze test, thereafter the mice received passive avoidance test. (b) Alternative ratio in Y maze test. (c) Total entry time in Y maze test. (d) Alternative ratio and (e) Total entry time in Y maze test of Aβ1–42 injected mice. (f) The latency time of acquisition trial. (g) The latency time of testing session. For (b,c,f,g), mice were injected Aβ25–35. n = 10 mice in each group. For (d,e), Aβ1–42 was ICV injected, n = 11–12 mice in each group. P < 0.05, ††P < 0.01 vs. control (sham). *P < 0.05, **P < 0.01 vs. Aβ ( + ). All values are expressed as mean ± S.E.. A1: B. breve A1, Don: Donepezil.
Figure 2
Figure 2
Change of gene expression profile in hippocampus of AD model mice by Bifidobacterium breve strain A1 treatment using RNA-seq analysis. Transcriptional analysis was performed on hippocampal tissues of sham-operated mice (SH), Aβ25-35 injected mice (AB) and mice treated with Aβ and B breve A1 (ABA). (a,b) Venn diagram of shared and unique hippocampal transcripts (a) in SH vs AB and/or SH vs ABA, and (b) in SH vs AB and/or AB vs ABA, p < 0.05 and FDR < 0.05. RNA-seq data from 5 mice are presented. (ce) GO Term enrichment analysis of differential expressed (DE) genes in AD hippocampus. Enrichment analysis of differential expressed genes (c) between Aβ-treated and control mice, (d) between groups with or without B. breve A1 administration and (e) using DAVID analysis.
Figure 3
Figure 3
Plasma SCFA levels of AD model mice. (a,b) Plasma SCFA levels of AD model mice for acetate (a) and for propionate and butylate (b). N = 4 for each group. *P < 0.05 vs. Aβ ( + ). All values are expressed as mean ± S.E.. A1: B. breve A1.
Figure 4
Figure 4
Effect of acetate treatment and non-viable Bifidobacterium breve A1 treatment on cognitive function in AD model mice. (a) Alternative ratio in Y maze test. (b) Total entry time in Y maze test. (c) The latency time of acquisition trial. (d) The latency time of testing session. Mice were injected Aβ25-35. n = 10 mice in each group. ††P < 0.01 vs. control. **P < 0.01 vs. Aβ ( + ). #P < 0.05, ##P < 0.01 vs. viable B. breve A1 group. All values are expressed as mean ± S.E.

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References

    1. Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984;120:885–90. doi: 10.1016/S0006-291X(84)80190-4. - DOI - PubMed
    1. McNaull BBA, Todd S, McGuinness B, Passmore AP. Inflammation and anti-inflammatory strategies for Alzheimer’s Disease – A mini-review. Gerontology. 2010;56:3–14. doi: 10.1159/000237873. - DOI - PubMed
    1. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. med. 2006;12:1005–1015. - PubMed
    1. Jack CR, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–128. doi: 10.1016/S1474-4422(09)70299-6. - DOI - PMC - PubMed
    1. Pistollato F, et al. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr. Rev. 2016;74:624–634. doi: 10.1093/nutrit/nuw023. - DOI - PubMed
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