The Oral–Gut–Systemic Axis in Periodontitis: Microbiome Dysbiosis, Immune Crosstalk and Translational Perspectives
4 affiliations
- 1Department of Periodontology, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland
- 2Department of Genetics, West Pomeranian University of Technology in Szczecin, Aleja Piastów 45, 70-311 Szczecin, Poland
- 3Department of Preclinical Conservative Dentistry and Preclinical Endodontics, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland
- 4Department of Periodontology and Operative Dentistry, University of Münster, 48149 Münster, Germany
Abstract
Periodontitis is a chronic inflammatory disease associated with subgingival dysbiosis and altered host response. Although it is usually considered a local disease of the tooth-supporting tissues, it may also interact with distant mucosal and systemic compartments. One possible explanation is the oral–gut–systemic axis. In this model, oral bacteria, microbial products and inflammatory mediators are swallowed and reach the gastrointestinal tract. In susceptible hosts, these signals may affect gut microbial ecology, epithelial barrier integrity, mucosal immunity and microbial metabolite pathways. Human studies show links between periodontitis, altered oral and gut microbial communities, oral–gut microbial signatures and systemic metabolomic changes. Experimental studies provide stronger mechanistic support. They suggest that periodontal pathogens, particularly Porphyromonas gingivalis, may promote gut dysbiosis, barrier dysfunction, endotoxemia, inflammasome activation, T helper 17/regulatory T cell (Th17/Treg) imbalance and changes in metabolite signaling pathways. Candidate pathways include aryl hydrocarbon receptor (AHR) signaling, suppression of G protein-coupled receptor 109A (GPR109A), short-chain fatty acid-related pathways and trimethylamine N-oxide (TMAO) metabolism. Inflammatory bowel disease is currently the most developed disease-specific model. Metabolic dysfunction-associated steatotic liver disease (MASLD), non-alcoholic fatty liver disease (NAFLD), rheumatoid arthritis, cardiometabolic metabolite pathways and gastrointestinal cancer models are less mature extensions. This review summarizes current evidence and identifies the need for longitudinal studies, strain-level source tracking, multi-omics, immune phenotyping and disease-specific intervention studies. At present, the concept is biologically plausible, but clinical translation remains premature.
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BibTeX
@article{mochol2026oralgutsystemic,
title = {{The Oral–Gut–Systemic Axis in Periodontitis: Microbiome Dysbiosis, Immune Crosstalk and Translational Perspectives}},
author = {Martyna Mochol and Hanna Kulig and Aleksandra Rączka and Mariusz Lipski and Ewa Marek and Laurentia Schuster and Till Dammaschke and Małgorzata Mazurek-Mochol},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209060},
url = {https://www.mdpi.com/1422-0067/27/20/9060},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Oral–Gut–Systemic Axis in Periodontitis: Microbiome Dysbiosis, Immune Crosstalk and Translational Perspectives
AU - Martyna Mochol
AU - Hanna Kulig
AU - Aleksandra Rączka
AU - Mariusz Lipski
AU - Ewa Marek
AU - Laurentia Schuster
AU - Till Dammaschke
AU - Małgorzata Mazurek-Mochol
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209060
UR - https://www.mdpi.com/1422-0067/27/20/9060
AB - Periodontitis is a chronic inflammatory disease associated with subgingival dysbiosis and altered host response. Although it is usually considered a local disease of the tooth-supporting tissues, it may also interact with distant mucosal and systemic compartments. One possible explanation is the oral–gut–systemic axis. In this model, oral bacteria, microbial products and inflammatory mediators are swallowed and reach the gastrointestinal tract. In susceptible hosts, these signals may affect gut microbial ecology, epithelial barrier integrity, mucosal immunity and microbial metabolite pathways. Human studies show links between periodontitis, altered oral and gut microbial communities, oral–gut microbial signatures and systemic metabolomic changes. Experimental studies provide stronger mechanistic support. They suggest that periodontal pathogens, particularly Porphyromonas gingivalis, may promote gut dysbiosis, barrier dysfunction, endotoxemia, inflammasome activation, T helper 17/regulatory T cell (Th17/Treg) imbalance and changes in metabolite signaling pathways. Candidate pathways include aryl hydrocarbon receptor (AHR) signaling, suppression of G protein-coupled receptor 109A (GPR109A), short-chain fatty acid-related pathways and trimethylamine N-oxide (TMAO) metabolism. Inflammatory bowel disease is currently the most developed disease-specific model. Metabolic dysfunction-associated steatotic liver disease (MASLD), non-alcoholic fatty liver disease (NAFLD), rheumatoid arthritis, cardiometabolic metabolite pathways and gastrointestinal cancer models are less mature extensions. This review summarizes current evidence and identifies the need for longitudinal studies, strain-level source tracking, multi-omics, immune phenotyping and disease-specific intervention studies. At present, the concept is biologically plausible, but clinical translation remains premature.
SN - 1422-0067
ER -