The Effect of PMPR and Chlorhexidine Mouthwash on Salivary and Acquired Enamel Pellicle (AEP) Proteins and Vascular Function in People with Periodontal Disease.

Periodontal diseases (PD) are inflammatory conditions in the mouth that cause degeneration of the tissues supporting teeth, including the gums, bone, and ligaments (Dubey & Mittal, 2020). PD extends beyond oral health; individuals with periodontitis face about a 19% increased risk of cardiovascular disease (CVD), underscoring the broader health implications associated with the condition (Dhadse et al., 2010). This strong association between PD and systemic diseases reflects the far-reaching health consequences of PD (Beck et al., 1996; Simpson et al., 2024). The causes of PD are multifactorial, including poor oral hygiene (Lertpimonchai et al., 2017), smoking (Borojevic, 2012), diabetes (Preshaw et al., 2012), genetic predispositions (Tettamanti et al., 2017), stress (Corridore et al., 2023), age (Clark et al., 2021), and certain medications (Nazir, 2017). Economically, PD has a global impact, costing $54 billion annually in direct treatments and $25 billion in indirect costs (Sanz et al., 2015; Simpson et al., 2024).

Professional mechanical plaque removal (PMPR) is a primary non-surgical treatment that removes supragingival and subgingival plaque, helping to stabilize attachment levels and reduce tooth loss in PD patients. For advanced cases, surgery becomes the necessary treatment (Darby, 2009; Boehm & Kim, 2024). Chemical plaque control with antiseptic rinses like chlorhexidine (CHX) can supplement PMPR by reducing bacterial load, though its long-term use is limited by side effects like staining and altered taste (Afennich et al., 2011; Brookes et al., 2020). While CHX is effective short-term for acute management of PD, S3 Level Clinical Practice Guidelines do not fully endorse it for active therapy due to mixed evidence (West et al., 2021).

Recent research shows that CHX not only disrupts the oral microbiome (Dejam et al., 2007; Kilian et al., 2016; Bescos et al., 2020; Bartsch et al., 2024; Simpson et al., 2024) but also interferes with the enterosalivary nitric oxide (NO) pathway, impacting vascular function by raising blood pressure, increasing vascular stiffness, and potentially causing myocardial hypertrophy (Lima et al., 2024; Mollace et al., 2023). Oral bacteria such as Actinomyces, Neisseria, and Rothia contribute to nitric oxide production, helping maintain vascular function and health (Hyde et al., 2014; Feng et al., 2023; Fejes et al., 2024). Recent findings indicate that individuals with PD have impaired nitrate reduction capacity (NRC), which may influence overall health and contribute to PD's systemic effects (Simpson et al., 2024).

Whole mouth saliva (WMS) contains proteins and organic molecules like glucose, urea, cortisol, mucin, albumin, statherin, and amylase, all essential for enamel integrity, lubrication, acid neutralization, and antimicrobial activity (Gurovich et al., 2009; Iorgulescu, 2009; Zimmerman, 2013; Mutahar et al., 2017; Pedersen et al., 2018). These components help form the acquired enamel pellicle (AEP), a protective layer that aids enamel remineralization and protects against acids (Siqueira et al., 2012; Vukosavljevic et al., 2014). Certain salivary proteins, such as matrix metalloproteinase-8 (MMP-8), are also key biomarkers for PD, aiding in diagnosis and monitoring progression (Ghallab, 2018).

In PD, there is an observable shift in the oral microbiome, characterized by an increase in disease-associated bacteria, such as the red-complex bacteria Porphyromonas gingivalis (Simpson et al., 2024), Tannerella forsythia (Bao et al., 2022), and Fusobacterium nucleatum (Groeger et al., 2022) (Kendlbacher et al., 2024). Saliva's antimicrobial proteins typically help regulate the oral microbiome, but this balance is disrupted in PD (Carpenter, 2020). The bacterial proteins produced by disease-associated bacteria include cysteine proteases (gingipains) and lipopolysaccharide (LPS) from Porphyromonas gingivalis (Hajishengallis, 2009); Bacteroides surface protein A (BsPA) from Tannerella forsythia (Bryzek et al., 2014), and adhesion proteins from Fusobacterium nucleatum (Fardini et al., 2011).

Saliva proteomics, the study of protein composition and function in saliva, offers a unique view into physiological health, as it enables easier tracking of biomarkers compared to blood tests. It can reveal diagnostic and prognostic markers that may improve patient outcomes and reduce healthcare costs (Dongiovanni et al., 2023). Although many proteomic studies have explored saliva proteins and biomarkers (Messana et al., 2013; Castagnola et al., 2017; Wazwaz et al., 2023), the protein profiles in WMS and AEP of individuals with PD, and their impact on vascular functions, remain unexplored. This study will apply proteomic analysis and bioinformatics, along with vascular assessments, to identify human and bacterial salivary protein profiles. Ultimately, it aims to link PD activity and tissue degradation patterns with cardiovascular changes.

The Connection Between Gum Disease, Heart Health, and Saliva

Gum disease, or periodontal disease (PD), is an inflammation of the gums and tissues supporting teeth. It develops when bacteria and plaque build up in the mouth, leading to the gradual breakdown of tissues around the teeth, including the gums, bones, and ligaments. Besides causing gum pain, bleeding, and even tooth loss, gum disease can impact overall health in surprising ways.

Why Gum Disease Is More Than Just an Oral Issue
Research shows that gum disease is not confined to the mouth—it’s linked to a higher risk of heart disease. People with advanced gum disease face an almost 20% increased risk of developing heart-related issues. Scientists think that gum disease may affect the whole body by promoting inflammation or by influencing blood pressure and blood vessel health.

What Causes Gum Disease?
Gum disease results from a combination of factors, including poor oral hygiene, smoking, diabetes, stress, and genetics. As a global health problem, it costs billions each year in treatments and productivity losses. The disease is usually managed by removing plaque with professional cleanings, but severe cases may need surgery. Additionally, antibacterial mouth rinses are sometimes used short-term, although long-term use is not recommended because of potential side effects and mixed evidence on effectiveness.

The Role of Saliva and Oral Bacteria
Saliva is more than just moisture; it’s rich in proteins and minerals that protect teeth by forming a layer called the enamel pellicle. This protective layer helps teeth stay strong by preventing damage from acids and aiding in natural repair. Saliva also helps balance the bacteria in our mouth, which is crucial for oral health. In gum disease, this bacterial balance shifts, allowing harmful bacteria to flourish while reducing helpful bacteria, including those that are key in supporting heart health.

How This Study Will Help
This research will examine the proteins in saliva and how they change with gum disease. The aim is to understand how gum disease may be influencing heart health through these changes in saliva and mouth bacteria. This study may help create better ways to detect and manage gum disease, not only to protect oral health but also to reduce the associated risks for heart disease.