Abstract
SummaryEvidence linking the gut-brain axis to Alzheimer’s disease (AD) is accumulating, but the characteristics of causally important microbes are poorly understood. We perform a fecal microbiome analysis in healthy subjects and those with mild cognitive impairment (MCI) and AD. We find that Faecalibacterium prausnitzii (F. prausnitzii) correlates with cognitive scores and decreases in the MCI group compared with the healthy group. Two isolated strains from the healthy group, live Fp360 and pasteurized Fp14, improve cognitive impairment in an AD mouse model. Whole-genome comparison of isolated strains reveals specific orthologs that are found only in the effective strains and are more abundant in the healthy group compared with the MCI group. Metabolome and RNA sequencing analyses of mouse brains provides mechanistic insights into the relationship between the efficacy of pasteurized Fp14, oxidative stress, and mitochondrial function. We conclude that F. prausnitzii strains with these specific orthologs are candidates for gut microbiome-based intervention in Alzheimer's-type dementia.
Highlights
50 million people have dementia, and nearly 10 million new cases of dementia occur every year.[1]
F. prausnitzii decreased in the mild cognitive impairment (MCI) group compared with the healthy group and correlated with cognitive test scores We first performed our own cross-sectional study to identify potential MCI-preventive microbes
We focused on microbes that were correlated with Montreal Cognitive Assessment Japanese version (MoCA-J) scores and abundant in the healthy group but decreased in the MCI group, and the correlation between the relative abundance of bacterial genera and the MoCA-J scores of the healthy and the MCI group was calculated
Summary
50 million people have dementia, and nearly 10 million new cases of dementia occur every year.[1]. We hypothesized that there would be a causal relationship between specific microbes and cognitive function in MCI, the prodromal stage of dementia, and that specific microbes would become promising candidates for gut microbiome-based preventive intervention in MCI
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