Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan

Abstract

We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.

Figure 1

Relative abundance of the bacterial types in the stool samples. Normal control (healthy controls), AD (individuals with Alzheimer's disease). (A) Phylum level, (B) class level, (C) genus level.

Figure 2

Violin plots of differentially abundant taxa between AD and healthy controls.

Figure 3

(A) α-diversity (Shannon, Simpson indexes) of fecal bacteria in individuals with Alzheimer's disease (AD) and normal controls. (B) β-diversity (weighted UniFrac distance) of fecal bacteria in individuals with Alzheimer's disease (AD) and healthy controls (Normal control). (C) The linear discriminant analysis (LDA) scores (LEfse plot). An LDA score (log 10) > 2 indicates a significantly different enrichment of bacteria taxa in the AD group (purple) compared to the control group (green). p phylum, c class, o order, f family, g genus, s species.

Figure 4

Correlation between adiponectin, C-reactive protein, total bilirubin, triglycerides, and differential bacterial taxa in AD and controls. ADPQ adiponectin, TBIL total bilirubin, CRP C-reactive protein, TRIG triglycerides.