基礎科学と病態生理

Longevity is influenced by a combination of genetic factors, lifestyle choices, and environmental conditions. These factors can alter microbiota composition, potentially influencing susceptibility to Alzheimer's disease (AD) and cognitive decline. We hypothesize that the microbiome in elderly individuals may be associated with different clinical stages of AD. This study aims to investigate the relationship between oral and gut microbiota composition in a Brazilian long-lived population and cognitive impairment within the AD continuum.

We conducted a pilot characterization of the oral and gut microbiota of 12 elderly individuals (>65 years) recruited by the Moriguchi Institute in Veranópolis, a longevity hotspot in southern Brazil. Participants underwent clinical-cognitive assessment, including the Clinical Dementia Rating (CDR), and were classified as cognitively unimpaired (CU), mild cognitive impairment (MCI), or Alzheimer's disease (AD). Saliva and fecal samples were sequenced using Illumina MiSeq™, targeting the V3-V4 regions of the 16S rRNA gene, and processed in R using DADA2. Amplicon sequence variants (ASVs) were inferred, and taxonomic assignments were performed with SILVA. Abundance data were used for alpha and beta diversity, and relative abundance analyses.

Alpha diversity was similar across groups, except for reduced salivary richness in MCI (Chao1, p = 0.002; Figure 1). Rarefaction curves indicated higher richness in the feces compared to saliva. PCoA analysis showed distinct group separations in feces, with MCI and AD being more similar, while saliva samples were more uniform. Relative abundance demonstrated alterations in phylum Bacillota, Bacteroidota, and Pseudomonadota in MCI and AD compared to the CU group (Figure 2). Changes were particularly evident in fecal families Lachnospiraceae, Bacteroidaceae, and Ruminococcaceae, and genus such as Bacteroides, Blautia, and Faecalibacterium. Notably, Streptococcus was almost exclusively elevated in fecal samples of the AD group. Saliva samples were more homogeneous across groups, though changes were observed in families Prevotellaceae and Streptococcaceae, and genus Prevotella, Streptococcus, Haemophilus, and Neisseria in MCI and AD compared to CU.

Fecal microbiota exhibited clinical-stage-specific changes, while salivary microbiota displayed more stability, underscoring microbial adaptations to the distinct. These findings highlight microbiome changes along the AD continuum, emphasizing the potential microbiome's role in healthy aging and resilience against neurodegeneration.