# The oral microbiome as a regulatory hub for systemic health: a systematic review of mechanistic links and clinical implications

**Authors:** Zhu Ling Guo, Ming Wang Cui, Yu Lei Dong, Shuai Wang

PMC · DOI: 10.1080/20002297.2026.2635233 · Journal of Oral Microbiology · 2026-03-03

## TL;DR

This review explores how the oral microbiome affects overall health and could be used for diagnosing and treating systemic diseases.

## Contribution

The paper systematically reviews mechanistic links between oral dysbiosis and various systemic diseases, highlighting clinical implications.

## Key findings

- Oral dysbiosis may influence systemic health through mechanisms like pathogen dissemination and inflammation.
- Oral microbiome changes are associated with diseases like cardiovascular disease, diabetes, and Alzheimer's.
- Non-invasive oral microbiome-based biomarkers and microbiome-modulating therapies show promise for disease management.

## Abstract

The human oral microbiome is a highly diverse ecosystem with important roles in oral and systemic health. Beyond dental caries and periodontitis, oral dysbiosis has been increasingly implicated in the development of multiple non-communicable diseases.

To systematically synthesize evidence on the mechanisms linking oral dysbiosis to systemic diseases and to summarize its diagnostic and therapeutic implications.

A systematic review was performed using major electronic databases. We screened 1,128 records and included 104 studies that met predefined eligibility criteria.

Evidence indicates that oral dysbiosis may influence systemic health through several mechanisms, including hematogenous dissemination of oral pathogens and virulence factors (e.g. lipopolysaccharide), chronic systemic inflammation, molecular mimicry in autoimmune disorders, and microbial metabolic byproducts. The reviewed studies support associations between oral microbiome alterations and atherosclerotic cardiovascular disease, type 2 diabetes, Alzheimer’s disease, rheumatoid arthritis, and gastrointestinal cancers. The literature also highlights the promise of non-invasive oral microbiome-based biomarkers for early detection and disease monitoring. Emerging microbiome-modulating interventions, including probiotics, prebiotics, and bacteriophage therapy, show potential for restoring oral eubiosis and improving systemic outcomes.

Oral dysbiosis is an important regulator of systemic disease processes and a promising target for diagnosis, prevention, and therapy. Integrating oral health and oral microbiome assessment into broader disease management may improve outcomes, although methodological standardization and stronger causal evidence are still needed.

## Linked entities

- **Diseases:** dental caries (MONDO:0005276), periodontitis (MONDO:0005076), type 2 diabetes (MONDO:0005148), Alzheimer’s disease (MONDO:0004975), rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PADI2 (peptidyl arginine deiminase 2) [NCBI Gene 11240] {aka PAD-H19, PAD2, PDI2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, PADI4 (peptidyl arginine deiminase 4) [NCBI Gene 23569] {aka PAD, PAD4, PADI5, PDI4, PDI5}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** atheroma (MESH:D058226), periodontal disease (MESH:D010510), cognitive decline (MESH:D003072), communicable (MESH:D003141), chronic diseases (MESH:D002908), T2DM (MESH:D003924), neuronal damage (MESH:D009410), IBD (MESH:D015212), gastrointestinal cancers (MESH:D005770), thromboembolic (MESH:D013923), oral (MESH:D020820), coronary artery disease (MESH:D003324), systemic (MESH:D015619), Cardiovascular diseases (MESH:D002318), infection (MESH:D007239), AMI (MESH:D009203), ischaemic stroke (MESH:D002544), bacteremia (MESH:D016470), citrullinated (MESH:C536207), gingivitis (MESH:D005891), bone destruction (MESH:D001847), insulin resistance (MESH:D007333), arthritis (MESH:D001168), dental caries (MESH:D003731), endotoxemia (MESH:D019446), RA (MESH:D001172), diabetic complications (MESH:D048909), hyperglycemic (MESH:D006944), Hypertension (MESH:D006973), ASCVD (MESH:D050197), CRC (MESH:D015179), Metabolic (MESH:D008659), Metabolic Dysregulation (MESH:D021081), OSCC (MESH:D000077195), systemic disease (MESH:D034721), neurofibrillary tangles (MESH:D055956), obesity (MESH:D009765), oral disease (MESH:D009059), Autoimmune disorders (MESH:D001327), carcinogenesis (MESH:D063646), non-communicable diseases (MESH:D000073296), Neurotoxicity (MESH:D020258), AD (MESH:D000544), cancer (MESH:D009369), endothelial dysfunction (MESH:D014652), Oral dysbiosis (MESH:D064806), diabetes (MESH:D003920), liver cirrhosis (MESH:D008103), Neuroinflammation (MESH:D000090862), Inflammation (MESH:D007249), chronic liver disease (MESH:D008107), Periodontitis (MESH:D010518), traumas (MESH:D014947), disease (MESH:D004194), neurodegenerative (MESH:D019636), metabolic syndrome (MESH:D024821), dyslipidemia (MESH:D050171), achlorhydria (MESH:D000126)
- **Chemicals:** alcohol (MESH:D000438), glucose (MESH:D005947), xylitol (MESH:D014993), calcium (MESH:D002118), SCFAs (MESH:D005232), CPC (MESH:D002594), sucrose (MESH:D013395), LPS (MESH:D008070), nitrite (MESH:D009573), arginine (MESH:D001120), carbohydrates (MESH:D002241), N-acetyldopamine (MESH:C006374), ADP-heptose (-), bile acids (MESH:D001647), sugar alcohols (MESH:D013402), citrulline (MESH:D002956), NO (MESH:D009569), cadaverine (MESH:D002103), AGEs (MESH:D017127), essential oils (MESH:D009822), triglycerides (MESH:D014280), TMAO (MESH:C005855), chlorine dioxide (MESH:C025109), sugars (MESH:D000073893), nitrate (MESH:D009566)
- **Species:** Streptococcus anginosus (species) [taxon 1328], Bacteriophage sp. (species) [taxon 38018], Limosilactobacillus reuteri (species) [taxon 1598], Prevotella melaninogenica (species) [taxon 28132], gut metagenome (species) [taxon 749906], Aspergillus (genus) [taxon 5052], Methanobrevibacter oralis (species) [taxon 66851], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Cladosporium (genus) [taxon 5498], Fusobacterium nucleatum (species) [taxon 851], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Candida [taxon 1535326], Tannerella forsythia (species) [taxon 28112], Homo sapiens (human, species) [taxon 9606], Porphyromonas gingivalis (species) [taxon 837], Leptotrichia (genus) [taxon 32067], Klebsiella (genus) [taxon 570], Nicotiana tabacum (American tobacco, species) [taxon 4097], Streptococcus salivarius K12 (strain) [taxon 1200793], Veillonella (genus) [taxon 29465], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Haemophilus (genus) [taxon 724], Streptococcus oralis (species) [taxon 1303], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Streptococcus mutans (species) [taxon 1309], Aggregatibacter actinomycetemcomitans (species) [taxon 714]

## Full text

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## Figures

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## References

104 references — full list in the complete paper: https://tomesphere.com/paper/PMC12958392/full.md

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Source: https://tomesphere.com/paper/PMC12958392