{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:31:26Z","timestamp":1789518686851,"version":"build-2803163510"},"reference-count":113,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: This study explores the link between oral biofluids, microbial dysbiosis, and Alzheimer\u2019s 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\u2013brain axis as a potential target for diagnosis, monitoring, and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/metabo15060389","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-7506","authenticated-orcid":false,"given":"Giuseppina","family":"Malcangi","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-2350","authenticated-orcid":false,"given":"Grazia","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-1039","authenticated-orcid":false,"given":"Alessio Danilo","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-025X","authenticated-orcid":false,"given":"Irma","family":"Trilli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1494-3519","authenticated-orcid":false,"given":"Laura","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6923-2102","authenticated-orcid":false,"given":"Lucia","family":"Casamassima","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9009-3575","authenticated-orcid":false,"given":"Paola","family":"Nardelli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-5883","authenticated-orcid":false,"given":"Francesco","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Palermo","sequence":"additional","affiliation":[{"name":"Departement of Experimental Medicine, University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-6337","authenticated-orcid":false,"given":"Angelo Michele","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Dipalma","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13195-019-0515-y","article-title":"Which features of subjective cognitive decline are related to amyloid pathology? 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