# The Oral Microbiome and Systemic Health: Current Insights into the Mouth–Body Connection

**Authors:** Ana Glavina, Dora Martić, Marija Ana Perko, Dora Mešin Delić, Antonija Tadin, Stjepanka Lešić, Daniela Šupe-Domić

PMC · DOI: 10.3390/life16020294 · 2026-02-09

## TL;DR

This review explores how the mouth's microbes can affect overall health, linking oral imbalances to diseases like heart disease and diabetes.

## Contribution

The paper provides a comprehensive synthesis of recent evidence on bidirectional interactions between oral microbiota and systemic diseases.

## Key findings

- Oral dysbiosis is associated with cardiovascular disease, diabetes, and adverse pregnancy outcomes.
- Links between oral microbiota and neurodegenerative disorders, kidney disease, and cancer are emerging.
- Proposed mechanisms include bacteraemia, inflammation, and immune disruption.

## Abstract

The oral cavity contains a complex and dynamic microbial ecosystem that plays a central role in maintaining both local and systemic homeostasis. Emerging evidence indicates that disturbances in oral microbial communities-including genetic and functional diversity within species-are associated not only with oral diseases but may also contribute to the development and progression of systemic diseases. This narrative review summarises the current state of knowledge on bidirectional interactions between oral microbial communities and major organ systems. A comprehensive search of PubMed/MEDLINE, Web of Science, Scopus, and Cochrane databases was conducted for studies published between 2019 and 2025, prioritising systematic reviews, meta-analyses, and high-quality mechanistic studies. Ultimately, 40 articles were included in the narrative synthesis. The results provide clear evidence of an association between oral dysbiosis and cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), chronic respiratory infections, and adverse pregnancy outcomes (APOs). Recent data also suggest links with neurodegenerative disorders, chronic kidney disease (CKD), autoimmune diseases, and cancer. Proposed mechanisms include transient or persistent bacteraemia, systemic inflammation caused by microbial metabolites and endotoxins, disruption of immune homeostasis, molecular mimicry, and modulation of host metabolic pathways. Despite growing evidence linking oral microbial communities to systemic health, most findings are based on observational studies, and causal relationships remain to be established through longitudinal and interventional research. Understanding the connection between the mouth and the body highlights the potential for targeting oral microbial activity, virulence factors, and host inflammatory responses in disease prevention and treatment.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), type 2 diabetes mellitus (MONDO:0005148), chronic kidney disease (MONDO:0005300), cancer (MONDO:0004992)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** OSCC (MESH:D000077195), lupus (MESH:D008180), systemic disease (MESH:D034721), hypoxia (MESH:D000860), metabolic dysregulation (MESH:D021081), ischaemia (MESH:D007511), renal decline (MESH:D006030), Metabolic Dysfunction (MESH:D008659), function (MESH:D003291), COPD (MESH:D029424), Colorectal Carcinogenesis (MESH:D063646), Pneumonia (MESH:D011014), oral and systemic cancers (MESH:D009062), respiratory failure (MESH:D012131), fatty liver (MESH:D005234), NOD (MESH:C566309), GDM (MESH:D016640), Autoimmune Diseases (MESH:D001327), oral diseases (MESH:D009059), Neurological and Neurodegenerative Disorders (MESH:D020271), hypoxic (MESH:D002534), head and neck cancer (MESH:D006258), pre-eclampsia (MESH:D011225), CKD (MESH:D051436), Neuroinflammation (MESH:D000090862), neuropsychiatric disorders (MESH:D001523), brain atrophy (MESH:C566985), AD (MESH:D000544), declining renal function (MESH:D060825), Lung Cancer (MESH:D008175), impaired glucose uptake (MESH:C536778), NAFLD (MESH:D065626), pulmonary disease (MESH:D008171), endothelial dysfunction (MESH:D014652), valvular lesions (MESH:D006349), Oral Dysbiosis (MESH:D064806), diabetes (MESH:D003920), Tumour (MESH:D009369), SjD (MESH:D012859), respiratory disease (MESH:D012140), PD (MESH:D010300), mitochondrial dysfunction (MESH:D028361), disease (MESH:D004194), neurodegeneration (MESH:D019636), Bacteraemia (MESH:C531821), injury to (MESH:D014947), Respiratory and Infectious Diseases (MESH:D012141), Inflammatory (MESH:D007249), MASLD (MESH:D008107), Periodontal (MESH:D010518), tooth loss (MESH:D016388), fibrosis (MESH:D005355), cardiometabolic disorders (MESH:D024821), pulmonary involvement (MESH:C566343), Autoimmune Susceptibility (OMIM:607836), Cognition (MESH:D003072), colonic (MESH:D003108), endothelial (MESH:D005642), Chronic hyperglycaemia (MESH:D002908), immune dysregulation (OMIM:614878)
- **Chemicals:** ethanol (MESH:D000431), nitrosamines (MESH:D009602), Nitric Oxide (MESH:D009569), 8-hydroxy-2-deoxyguanosine (MESH:D000080242), NO3- (MESH:C038619), sulphur compound (MESH:D013457), water (MESH:D014867), NO2- (MESH:D009585), uric acid (MESH:D014527), acid (MESH:D000143), Nitrate (MESH:D009566), ammonia (MESH:D000641), creatinine (MESH:D003404), ADMA (MESH:C018524), SCFA (MESH:D005232), ROS (MESH:D017382), RNS (MESH:D011886), tryptophan (MESH:D014364), alcohol (MESH:D000438), acetaldehyde (MESH:D000079), LPS (MESH:D008070), lipid (MESH:D008055), polyamine (MESH:D011073), propionate (MESH:D011422), fatty acid (MESH:D005227), MDA (MESH:D008315), Nicotine (MESH:D009538), butyrate (MESH:D002087), reactive nitrogen species (MESH:D026361), NADPH (MESH:D009249), urea (MESH:D014508), Nitrite (MESH:D009573), amino acid (MESH:D000596), ACPA (-), bile acid (MESH:D001647)
- **Species:** Nicotiana tabacum (American tobacco, species) [taxon 4097], Actinomyces (genus) [taxon 1654], Prevotella intermedia (species) [taxon 28131], Neisseria (genus) [taxon 482], Veillonella (genus) [taxon 29465], Streptococcus sanguinis (species) [taxon 1305], Haemophilus (genus) [taxon 724], Lactobacillus (genus) [taxon 1578], Campylobacter (genus) [taxon 194], Treponema denticola (species) [taxon 158], Aggregatibacter actinomycetemcomitans (species) [taxon 714], gut metagenome (species) [taxon 749906], Fusobacterium nucleatum (species) [taxon 851], Streptococcus mitis (species) [taxon 28037], Rothia mucilaginosa (species) [taxon 43675], Peptostreptococcus (genus) [taxon 1257], Homo sapiens (human, species) [taxon 9606], Tannerella forsythia (species) [taxon 28112], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Rothia (genus) [taxon 508215], Porphyromonas gingivalis (species) [taxon 837], Leptotrichia (genus) [taxon 32067]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941995/full.md

---
Source: https://tomesphere.com/paper/PMC12941995