Identification of Faecalibacterium prausnitzii strains for gut microbiome-based intervention in Alzheimer’s-type dementia

• DOI: 10.1016/j.xcrm.2021.100398
• Publication Date: 2021-09-14T14:32:46Z
• Authors: Atsushi Ueda; Shoji Shinkai; Hirotsugu Shiroma; Yu Taniguchi; Sayaka Tsuchida; Takahiro Kariya; Tomohiro Kawahara; Yodai Kobayashi; Noriyuki Kohda; Kazunari Ushida; Akihiko Kitamura; Takuji Yamada
• Keywords: Male; 0301 basic medicine; Medicine (General); gut microbiome-based intervention; Article; 03 medical and health sciences; mild cognitive impairment; R5-920; Cognition; Alzheimer Disease; Humans; Cognitive Dysfunction; RNA-Seq; microbiota-gut-brain axis; Aged; Principal Component Analysis; Amyloid beta-Peptides; Faecalibacterium prausnitzii; Brain; MCI; Gastrointestinal Microbiome; 3. Good health; Metabolome; Metagenome; Pasteurization; Dementia; Female; Alzheimer’s disease; Genome, Bacterial

Evidence 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.