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

Abstract

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.

Gut Microbiota Composition Is Related to AD Pathology

“…Five cross-sectional studies of differences in gut microbiota between patients with AD and controls found that several microbes were less abundant in AD, including Faecalibacterium prausnitzii, Eubacterium , Anaerostipes , Ruminococcus , and Roseburia spp, while other microbes, such as Odoribacter splanchicus , Bacteroides, Prevotella , and Alistipes spp., were more abundant ( 16 – 20 ). In line with these studies, we found that many of the highest ranked predictors for amyloid and p-tau status belonged to the Lachnospiraceae family, including Roseburia hominis , [Ruminococcus] torques, Lachnoclostridium, Monoglobus and Marvinbryantia spp.…”

“…We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21 [19][20][21][22][23][24]), 21 with MCI (64 ± 8 years, 43%F,) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29 [28][29][30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing.…”

“…In line with these animal studies, five human studies observed alterations in microbiota composition in patients with AD or mild cognitive impairment (MCI) compared to controls, with a lower abundance of SCFA-producing species in patients with AD (16)(17)(18)(19)(20). However, the nature of the specific microbiota alterations was conflicting across studies, with for instance lower (16,19,20) and higher (17) abundance of Ruminococcaceae spp., and lower (17) and higher (16,18,19) abundance of the Bacteroidetes phylum of MCI or AD patients compared to controls. In addition, former studies did not take into account AD pathology as measured with AD biomarkers (17)(18)(19)(20), while studies that did focused on a limited set of microbes for these analyses (16,21).…”

“…However, the nature of the specific microbiota alterations was conflicting across studies, with for instance lower (16,19,20) and higher (17) abundance of Ruminococcaceae spp., and lower (17) and higher (16,18,19) abundance of the Bacteroidetes phylum of MCI or AD patients compared to controls. In addition, former studies did not take into account AD pathology as measured with AD biomarkers (17)(18)(19)(20), while studies that did focused on a limited set of microbes for these analyses (16,21).…”

An Integrative Multiomics Approach to Characterize Prebiotic Inulin Effects on Faecalibacterium prausnitzii

“…In this study, integrative multiomics analysis was performed on proteins and metabolites, to identify the biological mechanism involved in the selective digestion of inulin in the intestine by F. prausnitzii. To investigate molecular-level cellular metabolic changes using multiomics approaches, we used F. prausnitzii strain A2-165, whose complete genome sequence has already been well reported (Miquel et al, 2013;Fitzgerald et al, 2018;Ueda et al, 2021). First, to confirm the preference for dietary carbohydrates in F. prausnitzii, we compared the growth of the bacterium in the presence of several carbon sources and confirmed significant growth in inulin.…”