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Review
. 2025 Jun 10;15(6):389.
doi: 10.3390/metabo15060389.

Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer's Disease

Giuseppina Malcangi  1 , Grazia Marinelli  1 , Alessio Danilo Inchingolo  1 , Irma Trilli  1 , Laura Ferrante  1 , Lucia Casamassima  1 , Paola Nardelli  1 , Francesco Inchingolo  1 , Andrea Palermo  2 , Angelo Michele Inchingolo  1 , Gianna Dipalma  1
Affiliations
Review

Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer's Disease

Giuseppina Malcangi et al. Metabolites. .

Abstract

Background: This study explores the link between oral biofluids, microbial dysbiosis, and Alzheimer's disease (AD), highlighting saliva and gingival crevicular fluid (GCF) as non-invasive diagnostic sources. AD onset and progression appear to be influenced not only by genetic and environmental factors but also by changes in the oral microbiome and related inflammatory and metabolic alterations. As global populations age, the incidence of AD is projected to rise significantly. Emerging evidence implicates the oral microbiome and salivary metabolites in neurodegenerative pathways, suggesting that oral health may mirror or influence brain pathology.

Materials and methods: A systematic review of recent multi-omics studies was performed, focusing on salivary and GCF analysis in patients with AD, those with mild cognitive impairment (MCI), and cognitively healthy individuals. Databases searched included PubMed, Web of Science, and Scopus, following PRISMA guidelines.

Results: Across the 11 included studies, significant alterations were reported in both the salivary microbiome and metabolome in AD patients. Notable microbial shifts involved increased abundance of Veillonella parvula and Porphyromonas gingivalis, while key metabolites such as L-tyrosine, galactinol, and mannitol were consistently dysregulated. These biomarkers correlated with cognitive performance and systemic inflammation.

Conclusions: Oral biofluids represent promising, accessible sources of biomarkers for early AD detection. Multi-omics integration reveals the oral-brain axis as a potential target for diagnosis, monitoring, and therapeutic strategies.

Keywords: Alzheimer’s disease; metabolome; oral microbioma; periodontal disease; saliva.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Interconnection between microbial dysbiosis and systemic health.
Figure 2
Figure 2
Link between periodontal disease and Alzheimer’s disease via the oral–brain axis. The arrows indicate proposed mechanisms linking periodontal inflammation to neurodegeneration: periodontal disease leads to systemic inflammation (↑ IL-1β, IL-6, TNF-α), which contributes to blood–brain barrier disruption. This promotes microglial activation and accumulation of amyloid-β and pTau181 in the brain, leading to cognitive decline. Bidirectional arrows highlight the diagnostic potential of salivary and gingival crevicular fluid biomarkers (e.g., ApoE, PgAgD), as well as the interplay between oral and neurological health.
Figure 3
Figure 3
PRISMA 2020 flow diagram. (“This PRISMA flow diagram was adapted from the PRISMA 2020 template (http://www.prisma-statement.org) under a CC BY 4.0 license.”) (accessed on 30 March 2025).
See this image and copyright information in PMC

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