Stratification of the Gut Microbiota Composition Landscape across the Alzheimer’s Disease Continuum in a Turkish Cohort Original paper

What was studied?

This study examined gut microbiota stratification in Alzheimer’s disease, using 16S rRNA sequencing to characterize microbial community structures across the Alzheimer’s disease (AD) continuum. The goal was to determine whether distinct microbiota subtypes exist in individuals with mild cognitive impairment (MCI) and AD compared with nondemented controls. The investigators applied multiple analytic approaches—including differential abundance testing, beta-diversity metrics, machine learning, Dirichlet multinomial mixtures, latent Dirichlet allocation, and topological data analysis—to identify reproducible ecological clusters. Across methods, two dominant microbiome configurations repeatedly emerged: Prevotella-dominant and Bacteroides-dominant communities. The study also explored how these microbial structures relate to disease severity, cognitive measures (MMSE and CDR), and key taxa that may serve as microbiome-based biomarkers.

Who was studied?

The cohort consisted of 125 Turkish adults: 47 with AD, 27 with amnestic MCI, and 51 nondemented controls, many of whom were spouses sharing similar dietary patterns. Participants were recruited from two university medical centers. Stool samples were collected, and clinical characterization included cognitive testing, education level, demographic information, medication profiles, and cerebrospinal fluid biomarkers for a subset of AD patients. This well-defined clinical stratification allowed the investigators to evaluate how microbiome composition maps onto stages of cognitive impairment while adjusting for confounders such as age, sex, and education.

Most important findings

Across all analytic strategies, the gut microbiota displayed robust stratification, driven primarily by Prevotella and Bacteroides. AD samples showed higher Proteobacteria (notably Escherichia/Shigella) and lower SCFA-producers such as Faecalibacterium. A Bacteroides-enriched “Bact2” enterotype—previously linked to inflammatory states—appeared prominently in a subset of AD participants.

The table below highlights the major microbial patterns consistently identified:

Key implications

This work demonstrates that the AD gut microbiome is not a single disease-associated signature but a structured microbial landscape dominated by reproducible Prevotella- and Bacteroides-based ecotypes. The identification of a Bact2-like inflammatory enterotype in AD suggests a mechanistic link between microbial dysbiosis and neuroinflammatory progression. These findings emphasize that precision nutrition and microbiome-targeted interventions must account for underlying microbiota stratification to avoid one-size-fits-all approaches. Moreover, specific taxa—particularly Prevotella, Bacteroides, Faecalibacterium, and Escherichia/Shigella—represent promising microbial candidates for inclusion in microbiome signature databases aimed at clinical translation.

Citation

Yıldırım S, Nalbantoglu OU, Bayraktar A, et al. Stratification of the gut microbiota composition landscape across the Alzheimer’s disease continuum in a Turkish cohort.mSystems. 2022;7(1):e00004-22