A comparison of the composition and functions of the oral and gut microbiotas in Alzheimer's patients

Abstract

Objective: Alterations in the oral or gut microbiotas have been reported in patients with subjective and mild cognitive impairment or AD dementia. However, whether these microbiotas change with the severity of the AD spectrum (mild, moderate, and severe AD) remains unknown. Thus, we compared alterations in the composition and gene functions of the oral and gut microbiota between different phases of AD.

Methods: We recruited 172 individuals and classified these into three groups: healthy controls (n = 40), a mild AD group (n = 43) and a moderate AD group (n = 89). Subgingival plaques and fecal samples were collected from all individuals. Then, we conducted 16S ribosomal RNA. sequencing to analyze the microbiotas.

Results: In order of the severity of cognition impairment (from normal to mild and to moderate AD), the oral abundances of the phyla Firmicutes and Fusobacteria showed a gradual upwards trend, while the abundance of the Proteobacteria phylum gradually decreased. In contrast, the abundance of the Firmicutes and Bacteroidetes phyla in the gut decreased progressively, while that of the Proteobacteria, Verrucomicrobia and Actinobacteria phyla increased gradually. Key differences were identified in the microbiomes when compared between the mild AD and moderate AD groups when applying the linear discriminant analysis effect size (LEfSe) algorithm. LEfSe analysis revealed alterations that were similar to those described above; furthermore, different bacterial taxa were associated with MMSE scores and age. KEGG analysis showed that the functional pathways associated with the oral microbiota were mainly involved in membrane transport and carbohydrate metabolism, while the gene functions of the fecal microbiota related to metabolism of amino acids, energy, cofactors and vitamins; identified significant differences among the three groups. Venn diagram analysis revealed that the number of genera that were present in both the oral and gut microbiota increased progressively from NC to mild AD and then to moderate AD.

Conclusions: This study is the first to report a comparative analysis of the oral and fecal microbiota of patients with mild and moderate AD. The compositions and functions of the oral and gut microbiotas differed when compared between different stages of AD.

Keywords: 16S ribosomal RNA; Alzheimer’s disease; gut microbiome; oral microbiome; oral-gut-brain axis.