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Review

The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction

by
Domenico Azzolino
1,*,†,
Margherita Carnevale-Schianca
2,†,
Luigi Santacroce
3,
Marica Colella
3,4,
Alessia Felicetti
5,
Leonardo Terranova
2,
Roberto Carlos Castrejón-Pérez
6,
Franklin Garcia-Godoy
7,8,9,
Tiziano Lucchi
1 and
Pier Carmine Passarelli
10
1
Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy
2
Respiratory Unit, Cystic Fibrosis Adult Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy
3
Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University Hospital of Bari, 70124 Bari, Italy
4
Doctoral School, eCampus University, 22060 Novedrate, Italy
5
Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
6
Instituto Nacional de Geriatría, National Institutes of Health, Ministry of Health, Ciudad de México 14080, Mexico
7
Bioscience Research Center, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA
8
The Forsyth Institute, Cambridge, MA 02142, USA
9
Department of Surgery, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
10
Department of Head and Neck and Sensory Organs, Division of Oral Surgery and Implantology, Fondazione Policlinico Universitario A. Gemelli IRCCS, University Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Nutrients 2025, 17(15), 2538; https://doi.org/10.3390/nu17152538 (registering DOI)
Submission received: 27 June 2025 / Revised: 30 July 2025 / Accepted: 30 July 2025 / Published: 1 August 2025
(This article belongs to the Special Issue Exploring the Lifespan Dynamics of Oral–Gut Microbiota Interactions)

Abstract

The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic health. The aim of this review is therefore to provide an overview of the interactions between oral and gut microbiota, and the influence of diet and related metabolites on this axis. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can migrate to the gut through the enteral route, particularly in individuals with weakened gastrointestinal defenses or conditions like gastroesophageal reflux disease, contributing to disorders like inflammatory bowel disease and colorectal cancer. Bile acids, altered by gut microbes, also play a significant role in modulating these microbiota interactions and inflammatory responses. Oral bacteria can also spread via the bloodstream, promoting systemic inflammation and worsening some conditions like cardiovascular disease. Translocation of microorganisms can also take place from the gut to the oral cavity through fecal–oral transmission, especially within poor sanitary conditions. Some metabolites including short-chain fatty acids, trimethylamine N-oxide, indole and its derivatives, bile acids, and lipopolysaccharides produced by both oral and gut microbes seem to play central roles in mediating oral–gut interactions. The complex interplay between oral and gut microbiota underscores their crucial role in maintaining systemic health and highlights the potential consequences of dysbiosis at both the oral and gastrointestinal level. Some dietary patterns and nutritional compounds including probiotics and prebiotics seem to exert beneficial effects both on oral and gut microbiota eubiosis. A better understanding of these microbial interactions could therefore pave the way for the prevention and management of systemic conditions, improving overall health outcomes.
Keywords: microbiome; oral microbiota; gut microbiota; gut dysbiosis; systemic diseases; inflammation; diet; probiotics; prebiotics microbiome; oral microbiota; gut microbiota; gut dysbiosis; systemic diseases; inflammation; diet; probiotics; prebiotics

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MDPI and ACS Style

Azzolino, D.; Carnevale-Schianca, M.; Santacroce, L.; Colella, M.; Felicetti, A.; Terranova, L.; Castrejón-Pérez, R.C.; Garcia-Godoy, F.; Lucchi, T.; Passarelli, P.C. The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction. Nutrients 2025, 17, 2538. https://doi.org/10.3390/nu17152538

AMA Style

Azzolino D, Carnevale-Schianca M, Santacroce L, Colella M, Felicetti A, Terranova L, Castrejón-Pérez RC, Garcia-Godoy F, Lucchi T, Passarelli PC. The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction. Nutrients. 2025; 17(15):2538. https://doi.org/10.3390/nu17152538

Chicago/Turabian Style

Azzolino, Domenico, Margherita Carnevale-Schianca, Luigi Santacroce, Marica Colella, Alessia Felicetti, Leonardo Terranova, Roberto Carlos Castrejón-Pérez, Franklin Garcia-Godoy, Tiziano Lucchi, and Pier Carmine Passarelli. 2025. "The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction" Nutrients 17, no. 15: 2538. https://doi.org/10.3390/nu17152538

APA Style

Azzolino, D., Carnevale-Schianca, M., Santacroce, L., Colella, M., Felicetti, A., Terranova, L., Castrejón-Pérez, R. C., Garcia-Godoy, F., Lucchi, T., & Passarelli, P. C. (2025). The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction. Nutrients, 17(15), 2538. https://doi.org/10.3390/nu17152538

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