Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer’s disease Original paper

What was studied?

This study investigated subgingival microbiome profiles in Alzheimer’s disease to clarify the relationship between periodontal dysbiosis, gingival crevicular fluid (GCF) metabolites, and amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Using 16S rRNA sequencing and untargeted LC–MS/MS metabolomics, the research mapped oral microbial composition and metabolic signatures across cognitively normal adults, individuals with aMCI, and patients with AD. The work advances the oral–brain axis hypothesis by pairing microbial community shifts with metabolite alterations linked to cognitive decline, identifying species–metabolite clusters that may serve as early diagnostic biomarkers of AD progression.

Who was studied?

Ninety-six adults were enrolled in this cross-sectional analysis: 32 cognitively normal controls, 32 participants with aMCI, and 32 with clinically diagnosed AD. All individuals underwent standardised neurological examinations and comprehensive periodontal assessment, including clinical attachment loss, probing depth, plaque index, and bleeding on probing. Subgingival plaque and GCF samples were collected from Ramfjord index teeth and pockets with depth >3 mm. Participants were screened carefully to exclude confounders such as diabetes, recent antibiotic exposure, active infections, immunosuppression, or recent periodontal treatment. This produced a well-defined clinical gradient from normal cognition to aMCI to AD, with corresponding gradations in periodontal disease severity.

Most important findings

The study revealed pronounced microbial and metabolic distinctions across cognitive groups. β-diversity analyses demonstrated clear structural separation of subgingival communities among controls, aMCI, and AD. Sixteen species correlated significantly with cognitive status. AD-associated taxa included Veillonella parvula, Dialister pneumosintes, Prevotella melaninogenica, Megasphaera micronuciformis, Anaeroglobus geminatus, Streptococcus anginosus, and Campylobacter gracilis, all showing higher abundance with worsening cognition. Species enriched in cognitively normal individuals—Pseudoleptotrichia goodfellowii, Leptotrichia buccalis, Actinomyces massiliensis, Streptococcus sanguinis, and Haemophilus parainfluenzae—declined across aMCI and AD. Metabolomic profiling identified 165 differentially abundant GCF metabolites. Key metabolic pathways altered in AD included purine metabolism, galactose metabolism, lysine degradation, and amino sugar pathways. Integrative DIABLO analysis revealed strong correlations between AD-enriched species (V. parvula, D. pneumosintes) and metabolites such as galactinol, sn-glycerol-3-phosphoethanolamine, D-mannitol, L-iditol, and 1h-indole-1-pentanoic acid-3-(1-naphthalenylcarbonyl). These metabolites demonstrated excellent diagnostic accuracy (AUC > 0.98) for distinguishing AD from aMCI and controls.

Key implications

This study strengthens evidence for a microbiome-driven oral–brain axis by demonstrating that AD is associated with distinctive periodontal microbial dysbiosis and corresponding metabolic disturbances in GCF. The identified species–metabolite pairs may serve as early biomarkers for cognitive decline, and GCF emerges as a practical, noninvasive biofluid for AD risk assessment. Findings suggest that periodontal health may influence or mirror neurodegenerative processes, highlighting the potential role of oral microbial signatures in precision diagnostics for AD.

Citation

Qiu C, Zhou W, Shen H, et al. Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer’s disease.Alzheimer’s Research & Therapy. 2024;16:41. doi:10.1186/s13195-024-01402-1