2.1 Diabetes and periodontal diseases

Robust epidemiological and clinical evidence substantiates the association between the two.^20-22 Diabetic patients exhibit a significantly higher prevalence of periodontitis and show worse periodontal parameters, including clinical attachment loss, periodontitis surface area, and the number of teeth lost.^{20, 54-58} Conversely, individuals with periodontitis are at an increased risk of developing diabetes.⁶

A recent study delineated the pathophysiological mechanisms through which diabetes impacts periodontal disease, encompassing vascular alterations in the gingiva, immune responses, collagen metabolism disorders, and specific microbiological profiles within periodontal pockets. Similarly, the mechanisms by which periodontal disease may affect diabetes include increased serum oxidative stress markers, elevated inflammatory markers, and enhanced insulin resistance.²¹ In 2023, Zhao et al. identified six potential mechanisms underlying the interaction between periodontitis and diabetes (Figure 2): (1) microbial factors; (2) enhanced inflammatory response through cytokines, adipokines, advanced glycation end product/receptor for advanced glycation end product (AGE/RAGE) pathways, and miRNAs; (3) host immune factors; (4) oxidative stress; (5) alveolar bone resorption damage; and (6) epigenetic changes.²⁴ Later, Enteghad et al. added that the uncoupling of resorptive and formative responses in connective tissue.²⁰ To provide a novel perspective on the interaction between diabetes and periodontitis, we reviewed the literature pertaining to the underlying mechanisms (Table 2) utilizing key molecules that may play significant roles in both diseases as indicators.

With the advancement of various saliva-based methodologies, markers, and models for the clinical screening of diabetes and prediabetes, saliva has emerged as a promising medium for this purpose. Dentists may leverage noninvasive chairside techniques to screen or diagnose diabetes and collaborate effectively with internists to manage the oral health of diabetic patients. Studies have demonstrated that placental growth factor (PlGF)⁵⁹ in gingival crevicular fluid (GCF) and microbial components⁶⁰ in saliva are correlated with blood glucose levels. These findings offer a promising avenue for the noninvasive auxiliary diagnosis of DM. In addition, researchers have developed diagnostic models capable of screening for prediabetes and diabetes in patients with periodontitis,⁶¹ demonstrating moderate to good discriminative ability. In the future, dental clinics may assume an increasingly vital role in diabetes screening.

2.2 Diabetes and dental implants

Dental implants represent an effective solution for the replacement of missing teeth; however, their success is contingent upon both the local periodontal conditions and the overall health of patients, particularly with respect to a history of diabetes. Ongoing discussions examine how diabetes influences dental implant outcomes, with some researchers suggesting that diabetes may lead to complications surrounding implants and impede bone healing, ultimately resulting in a lower surgical success rate.^109-111 Even if the initial success rates for implants in diabetic individuals can be quite high, the long-term results often seem less promising.¹¹² Conversely, other studies report differing results, indicating that the implant success rate remains within an acceptable range.^113-118 This inconsistency may stem from variations in diagnostic criteria and other influencing factors, particularly differences in the glycemic control of the studied patients.^{38-40, 42, 119} The evidence derived from two recently published meta-analyses indicates that the management of blood glucose levels is a critical factor influencing the success of implants in diabetic patients.^{41, 120}

The mechanisms through which diabetes influences dental implants are analogous to its effects on osteogenesis and osteoclastogenesis.¹²¹ A review conducted by de Oliveira et al. delineated these mechanisms as follows: (1) disrupting the balance between bone resorption and synthesis; (2) inducing microvascular disease; and (3) diminishing markers of bone formation while affecting collagen structure.¹²² Furthermore, AGEs-related NOX (NADPH oxidases)-mediated oxidative stress significantly impairs bone healing in diabetic patients.¹²³

Future improvements in the success rates of dental implants for diabetic patients are expected to focus on enhancing implant material properties,³⁷ refining implant coatings,¹²⁴ and advancing surgical techniques.¹²⁵

2.3 Diabetes and apical periodontitis

AP manifests at the apex of the tooth root, leading to inflammation in both dental and periodontal tissues. Root canal therapy (RCT) serves as the primary treatment modality. Although evidence remains limited, existing studies indicate a positive correlation between diabetes and the prevalence of AP lesions.⁴³ Poor blood glucose control can lead to higher rates of AP and increased failure rates of RCT.^126-129 The impact of RCT on blood glucose management in diabetic patients is still under debate.^130-132 The discrepancies in findings may be attributed to differences in criteria, limited sample sizes, or varying follow-up periods. Further well-structured, large-scale clinical trials are needed.

Existing evidence suggests that diabetes may exacerbate both the incidence and progression of AP by modulating levels of inflammatory factors, oxidative stress, and the prevalence of Candida albicans (C. albicans) within periodontal tissues. Several animal studies have underscored the significant roles of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) in the pathogenesis and progression of both diabetes and AP.^{68, 133} Furthermore, diabetes is known to disrupt the antioxidant balance by elevating malondialdehyde (MDA) and uric acid levels while concurrently decreasing albumin concentrations. The presence of AP exacerbates these diabetic effects, leading to further reductions in albumin and increases in uric acid levels.¹³⁴ Additionally, another investigation demonstrated that the presence of C. albicans in type 2 diabetes mellitus (T2DM) individuals correlates with a higher incidence of AP.¹³⁵

2.4 Diabetes and tooth extraction

Persistent hyperglycemia and chronic inflammation associated with DM can adversely affect the healing process of extraction sockets.^136-138 This underscores the importance of blood glucose control for diabetic patients undergoing tooth extraction. However, many oral surgeons remain uncertain about the critical thresholds for blood glucose and HbA1c levels, as well as the point at which the risk of adverse complications significantly escalates.¹³⁹ A systematic review has provided new insights, indicating that a fasting blood glucose level of 240 mg/dL serves as the critical threshold for any dental treatment, as warning signs of diabetes begin to manifest at this level. For diabetic patients, the maximum acceptable blood glucose levels prior to tooth extraction are 180 mg/dL before meals and 234 mg/dL 2 h postprandially.¹⁴⁰ Moreover, the use of prophylactic antibiotics is not sufficiently supported by evidence. T2DM does not necessitate prophylactic antibiotics prior to tooth extraction in the absence of acute odontogenic infections.¹³⁸ A systematic review indicates that there is currently no scientific evidence to substantiate the efficacy of prophylactic antibiotic use prior to dental surgery in patients with diabetes.¹⁴¹

The characteristics of diabetic wounds encompass elevated levels of ROS, impaired M1/M2 macrophage polarization, and chronic inflammation driven by proinflammatory chemokines.¹³⁹ The challenges associated with healing postextraction wounds are linked to diminished osteogenic differentiation of mesenchymal stem cells (MSC),¹⁴² activation of matrix metalloproteinase-9 (MMP-9), persistent imbalance in the receptor activator of nuclear factor-κ B ligand (RANKL)/osteoprotegerin (OPG) ratio.¹⁴³ Furthermore, the hyperglycemic environment disrupts the secretion of cytokines such as TNF-α, IL-6, and IL-1β from macrophages,¹⁴⁴ resulting in functional impairments in neutrophils during the inflammatory response stages of wound healing, including migration, chemotaxis, and adhesion.¹³⁸

2.5 Diabetes and head and neck cancer

HNCs encompass a range of malignancies originating in regions such as the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity, salivary glands, and lymph nodes within the head and neck area.¹⁴⁵ Among these, cancers directly impacting the oral cavity and adjacent areas, such as oral squamous cell carcinoma (OSCC) and oropharyngeal carcinoma, are of particular concern due to their profound implications for oral health and systemic well-being. Besides, for advanced-stage cancers, the application of high-energy radiation can lead to various potentially severe oral complications, including reduced salivary secretion causing xerostomia, oral pain, bacterial and fungal infections, taste disturbances, swallowing difficulties, discomfort, bleeding of periodontal tissues, and speech impairments.^{146, 147} This section focuses on the relationship between the aforementioned cancers that directly affect oral health and chronic diseases, as well as the impact of cancer treatments and medications on chronic conditions.

DM has been associated with an increased risk of developing various cancers, including HNC.^{46, 47, 148} T2DM promotes proliferation, metastasis, and inhibits apoptosis in OSCC.¹⁴⁹ Patients with oral and oropharyngeal cancers who have a history of diabetes may have lower survival rates.¹⁵⁰

Researches indicate that antidiabetic medications such as metformin,⁴⁶ pioglitazone,¹⁵¹ and SGLT-2 inhibitors^{152, 153} exhibit antitumor effects. A review has elucidated the mechanisms of action of SGLT-2 inhibitors and their applications in the management of type 2 diabetes and its associated complications. Both SGLT1 and SGLT2 are expressed in various tumors, where they facilitate euglycemic glycolysis by supplying tumor cells with glucose. Furthermore, the proliferation of carcinomas expressing SGLT2 can be effectively inhibited through the administration of an SGLT2 inhibitor.¹⁵⁴ Besides, the effects ofGLP-1 receptor agonists (GLP-1RAs) on tumors remain ambiguous, with some studies suggesting a potential increase^{155, 156} in cancer risk and others indicating otherwise.^{157, 158} Additional experiments are warranted to investigate.

The association between diabetes and HNC may be attributed to shared risk factors inherent to both conditions.¹⁵⁹ A review published in 2020 delineated the potential mechanisms by which diabetes may influence the occurrence, metastasis, and prognosis occ. These mechanisms include hyperglycemia, hyperinsulinemia, insulin resistance, chronic inflammation, and immune dysfunction.⁴⁶

2.6 Diabetes and salivary gland diseases

In recent years, accumulating evidence has established a robust association between salivary gland diseases and diabetes.¹⁶⁰ Salivary gland dysfunction in diabetic patients is predominantly characterized by impaired salivary secretion, resulting in diminished saliva flow, a sensation of dry mouth, and an elevated risk of dental caries.^{161, 162} Considering that the management of xerostomia should prioritize addressing its underlying causes,¹⁶³ effective blood glucose control is essential for diabetic patients experiencing this condition. When indicated, local saliva substitutes and/or stimulants may be utilized as adjunctive therapies.

Nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) have been identified as promising targets for mitigating the reduced salivary secretion associated with diabetes-induced xerostomia.¹⁶⁴ Immunohistochemical analyses of diabetic rats further elucidate that inflammation and oxidative stress are critical contributors to the progression of this condition.¹⁶⁵ Additionally, acinar cell vacuolation,¹⁶⁶ intracellular structural damage,¹⁶⁷ and dysfunction of the cholinergic vasodilation pathway¹⁶⁸ have been implicated as potential mechanism.

Novel approaches have emerged to alleviate xerostomia and enhance salivary secretion in diabetic patients. Wu et al. reported that sialography-guided injection of pancreatic lipase into the salivary glands can effectively mitigate diabetes-related chronic obstructive parotitis.¹⁶⁹ Additionally, Muhamed et al. confirmed the efficacy of a topical saliva stimulant spray containing 1% malic acid for treating xerostomia in patients with T2DM.¹⁷⁰ Furthermore, animal studies have demonstrated that both atropine and metformin can ameliorate salivary gland damage in diabetic rats and alleviate symptoms of xerostomia, with effects being particularly pronounced when used in combination.¹⁷¹ These findings may offer new insights and strategies for the clinical management of diabetic xerostomia.

2.7 Diabetes and dental caries

Diabetic patients exhibit a heightened risk of developing dental caries,¹⁷² which is influenced by their glycemic control and the duration of diabetes.¹⁷³ Two meta-analyses have explored the relationship between diabetes and dental caries. One analysis revealed that the overall prevalence of dental caries in children and adolescents with type 1 diabetes was 67%, with the highest prevalence observed in South America and the lowest among patients maintaining good metabolic control.¹⁷⁴ The other study indicated that type 2 diabetes may contribute to an increase in the incidence of caries among adults.⁵⁰

The mechanisms underlying the association between diabetes and dental caries remain inadequately explored; however, they may be related to the effects of diabetes on saliva flow rate and buffering capacity, as well as alterations in the oral microbiota of affected individuals. Research has demonstrated that individuals with diabetes exhibit elevated levels of Lactobacillus alongside diminished saliva flow and buffering capacity. These factors facilitate the proliferation of Streptococcus mutans, thereby increasing the risk of dental caries.^{175, 176}

2.8 Diabetes and root fracture

Root fracture refers to a break or crack in the root of a tooth. The incidence of vertical root fracture (VRF) in diabetic patients is 2.67 times higher than that observed in nondiabetic individuals.¹⁷⁷ Furthermore, the resistance to root fracture in the premolars of diabetic patients is significantly lower compared to their nondiabetic counterparts.¹⁷⁸

The impact of diabetes on the physiological structure of teeth may be related to the increased incidence of root fracture in diabetic patients. Research has found that diabetes can disrupt enamel development, leading to alterations in its microstructure and mechanical properties.¹⁷⁹ Additionally, diabetes affects the nanostructure of dentin, with concentrations of elements such as magnesium, zinc, strontium, lithium, manganese, and selenium being significantly lower than those in nondiabetic patients, while copper concentrations are higher in diabetic patients.¹⁸⁰

3.1 RA and periodontitis

Over the past decade, numerous studies worldwide have confirmed the correlation between RA and periodontitis.^197-200 On one hand, certain RA medications appear to elevate the risk of periodontal inflammation and exacerbate periodontitis.^{201, 202} Conversely, periodontal treatment has been shown to reduce RA activity.^{181, 203, 204} The mechanisms by which RA influences periodontitis primarily involve microbial factors, inflammatory mediators, and genetic associations (Figure 3).

Patients with periodontitis and RA often exhibit an abnormal abundance of specific microorganisms,^{205, 206} along with limited variation in microbial taxa and gene functions between deep and shallow subgingival sites.²⁰⁷ These findings suggest that RA may influence the development and progression of periodontitis through alterations in the microbiome. Furthermore, specific oral pathogens such as Porphyromonas gingivalis (P. gingivalis) produce peptidyl arginine deiminase (PPAD),²⁰⁸ which can citrullinate proteins, resulting in the formation of citrullinated autogenic antigens (CPAs) and subsequently leading to the production of anti-citrullinated protein antibodies (ACPAs).²⁰⁹

Furthermore, RA and periodontitis share common molecular mediators, such as MMP-8, IL-6, and prostaglandin E2.^{210, 211} These same mediators may play a role in their interaction. RA can also influence periodontitis by regulating inflammatory factors through various upstream mediators. Studies have shown that nicotinamide phosphoribosyl transferase (NAMPT) expression is upregulated in the periodontal ligament tissues of RA mice, resulting in elevated levels of proinflammatory cytokines (IL-6), chemokines (IL-8, CCL5), and inflammatory mediators such as COX-2, MMP-1, and MMP-3 in periodontal ligament cells.²¹² Another study suggests that cathepsin K (Ctsk) influences the infiltration of dendritic cells and T cells, as well as the production of inflammatory factors through the TLR9 signaling pathway, serving as a key pathological regulator in both RA and periodontitis. This mechanism contributes to enhanced erosion of periodontal bone and knee cartilage.²¹³

In addition to the aforementioned microbial and inflammatory factors, other studies have explored genetic associations. It was found that IL-1α-889 C/IL-1β-511a is positively correlated with RA.²¹⁴ Furthermore, another study indicated that a high incidence and severity of periodontitis in first-degree relatives (FDRs) of RA patients are associated with seropositivity for ACPAs, further supporting the hypothesis that periodontitis may serve as a risk factor for the development of RA.²¹⁵

3.2 RA and other oral diseases

4.1 Atherosclerotic vascular disease and periodontal diseases

Atherosclerotic vascular disease (ASVD) is a chronic condition characterized by the accumulation of lipids, cholesterol, and other substances within the arterial walls, leading to the formation of atherosclerotic plaques.²²⁷ There is a significant increase in risk associated with chronic periodontitis and ASVD, independent of other established cardiovascular risk factors.²²⁸ Meta-analyses encompassing prospective cohort studies, case–control studies, and cross-sectional studies consistently demonstrate a markedly elevated risk of coronary heart disease (CHD) in patients with periodontal disease.⁷ Furthermore, periodontal disease increases the incidence of myocardial infarction by two to four times,²²⁹ while severe periodontal disease can elevate the risk of stroke by 3.5%.²³⁰

The underlying mechanisms linking ASVD and periodontitis primarily involve infection, molecular mimicry, and systemic inflammation (Figure 4).²³¹ Furthermore, numerous lines of evidence suggest a potential association between P. gingivalis and atherosclerotic diseases related to periodontal disease. First, P. gingivalis can invade cardiovascular cells,²³² with its distant invasion correlating with an increased risk of acute myocardial infarction,²³³ indicating that it may exacerbate the severity of coronary artery disease through the induction of systemic inflammation. Second, P. gingivalis degrades platelet endothelial cell adhesion molecules (PECAM-1) and vascular endothelial cadherin (VE-cadherin), compromising the integrity of the endothelial barrier and enhancing vascular permeability.²³⁴ This disruption may promote platelet aggregation and the release of proinflammatory cytokines, potentially accelerating the progression of atherosclerosis.²³⁵ Additionally, the presence of P. gingivalis is often associated with significantly elevated levels of antibodies against human heat shock protein 60 (HSP60).²³⁶ Under conditions characterized by endothelial dysfunction, HSP60 expression is observed; its epitopes share similarities with GroEL protein from P. gingivalis,²³⁷ which may lead to cross-reactivity that further exacerbates endothelial damage and accelerates atherosclerosis.

4.2 Hypertension and periodontal diseases

Hypertension is a prevalent risk factor for CVDs, affecting approximately 45% of the global population, with prevalence rates increasing with age.²³⁸ Notably, about 50% of hypertensive patients fail to achieve effective blood pressure control.^{239, 240} This high prevalence can largely be attributed to a lack of public awareness regarding the classic triggers of hyperadherence to treatment recommendations among patients.²⁴¹ However, it is crucial to consider that nonclassical cardiovascular risk factors, such as periodontitis, may also contribute to the onset and poor management of hypertension.²⁴²

Clinical data and systematic reviews indicate that patients with periodontal disease exhibit significantly higher systolic and diastolic blood pressure compared to those without the condition,²⁴³ with a notable association between moderate to severe periodontal disease and an increased risk of hypertension.²⁴⁴ Furthermore, there is a significant correlation among periodontal disease, the number of missing teeth, and the experience of basic periodontal treatment concerning future incidence of hypertension.²⁴⁵ Despite considerable heterogeneity across studies, current evidence suggests that periodontal treatment is associated with a marked reduction in C-reactive protein (CRP) levels and an improvement in endothelial function, along with varying degrees of blood pressure reduction.^{11, 246, 247}

The pathogenesis of hypertension in patients with periodontitis is complex and not yet fully elucidated, involving multiple interconnected mechanisms. For instance, inflammatory responses characterized by elevated levels of inflammatory molecules during periodontitis impair endothelial function and contribute to increased blood pressure (Figure 4).^{241, 248, 249} Immune cell responses are also significant; activated T cells migrate to vascular tissues, releasing proinflammatory cytokines that lead to vascular dysfunction.^249-251 Additionally, microbial dysbiosis in the oral cavity, marked by pathogenic bacteria associated with periodontitis, correlates with elevated blood pressure.^252-254 Finally, noncoding RNAs, particularly microRNAs, may serve as epigenetic regulators linking periodontitis and hypertension.²⁵⁵

4.3 Other oral diseases

In addition to periodontitis, patients with CVDs demonstrate a higher incidence of dental caries and tooth loss.^{228, 256, 257} The loss of five or more teeth is significantly associated with an increased risk of CHD events and acute myocardial infarction. When the number of missing teeth reaches nine or more, there is a notable association with the risk of CVDs, diabetes, and all-cause mortality.²⁵⁸ A meta-analysis revealed a linear relationship between tooth loss and CHD mortality.²⁵⁹

5.1 COPD

Patients with COPD often exhibit poorer oral health, as evidenced by worse periodontal status, higher plaque indices, and elevated DMFT (decayed, missing, filled teeth) scores.²⁶⁶ Poor oral conditions or diseases, such as periodontitis,^{267, 268} dental caries,²⁶⁴ and tooth loss²⁶⁹ can exacerbate airflow limitation in COPD patients, worsening daily respiratory symptoms like coughing and wheezing and potentially contributing to acute exacerbations that lead to increased hospitalization rates and higher mortality. Direct evidence demonstrating that oral care interventions can improve outcomes in COPD is currently limited; however, two small-scale trials have suggested that periodontal treatment may reduce the frequency of COPD exacerbations.^{12, 270}

Research on the mechanisms linking COPD and various oral diseases is limited, with many studies conducted using animal models. These mechanisms may involve immune responses, microbial factors, and ferroptosis (Figure 5). Mutual exacerbation of periodontitis and COPD is associated with the activation of γδ T cells and M2 macrophages, ultimately leading to increased expression of IL-17 and interferon gamma (IFN-γ), as well as M2 macrophage polarization.²⁷¹ Furthermore, P. gingivalis or Fusobacterium nucleatum (F. nucleatum) promoted the development of COPD and impaired lung function in mice.²⁷² Studies have also shown that periodontitis accelerates the progression of COPD by upregulating ferroptosis in lung tissue.²⁷³

5.2 Bronchial asthma (asthma)

Patients with asthma exhibit altered salivary flow rates and composition, as well as poorer oral health, characterized by a higher prevalence of dental caries.^{274, 275} Medications, such as inhaled corticosteroid (ICS) therapy used to treat bronchial asthma are also associated with an increased incidence of dental caries.²⁷⁶ The heightened risk of dental caries linked to ICS may be attributed to changes in salivary composition and flow rate.²⁷⁷ Furthermore, clinical data and systematic reviews indicate that asthma patients may have an elevated risk of periodontitis^{278, 279} and tooth loss.²⁸⁰

Currently, there is no conclusive evidence establishing a direct biological link between periodontitis and asthma. The prevailing theoretical framework posits that these two inflammatory diseases may influence one another through microbial interactions, inflammatory factors, and immune responses (Figure 5). Research has shown that the periodontal pathogen Prevotella can induce the production of matrix metalloproteinases (MMPs), which adversely affect both periodontitis and asthma.²⁸¹ Additionally, MMPs can be produced by various inflammatory cells in the respiratory tract, potentially exacerbating periodontal inflammation.²⁸² On the immunological front, periodontal pathogens activate host immune cells to produce cytokines such as prostaglandin E2 (PGE2), interferon-γ, TNF-α, and several interleukins (IL-1, IL-6, IL-10, IL-11). These cytokines stimulate macrophages and osteoclasts to release hydrolases and collagenases—enzymes that degrade collagen and elastic fibers in lung tissue—thereby contributing to bronchial remodeling processes in asthma.²⁸³ Moreover, Th17 cells are implicated in various immune-mediated inflammatory conditions such as psoriasis and RA; they serve as potent mediators of tissue inflammation. Interleukin 17A (IL-17A) can activate a range of inflammatory cascades that mediate the development and progression of periodontitis along with related systemic chronic inflammatory diseases like asthma.²⁸⁴

5.3 Pneumonia

Epidemiological studies have demonstrated a correlation between oral health issues and the risk of developing pneumonia. Data from the Korean national population indicate that oral health problems, such as dental caries and tooth loss, significantly increase the risk of pneumonia; frequent tooth brushing and regular professional dental cleanings are associated with a reduced incidence of this condition.²⁸⁵ In specific populations, including intensive care unit (ICU) patients,²⁸⁶ adults with severe and complex neurological disorders,²⁸⁷ postoperative cancer patients,²⁸⁸ and acute stroke patients,²⁸⁹ professional oral care has been linked to a decrease in pneumonia incidence. When examining specific types of pneumonia, evidence supporting the link between oral health is more consistent for hospital-acquired pneumonia (HAP),^{290, 291} whereas the association with community-acquired pneumonia (CAP) remains controversial.^292-295

Regarding the potential mechanisms linking oral health to the development of various types of pneumonia, Kim et al. proposed that the oral environment can serve as a reservoir for pneumonia pathogens, which may be aspirated into the lower respiratory tract under certain conditions, thereby creating a favorable environment for pneumonia development.²⁹³ Recent studies have reaffirmed that oral bacteria can act as a source of infection in aspiration pneumonia, with the quantity of oral bacteria identified as a significant risk factor for this condition.^{296, 297} Furthermore, inflammatory cytokines induced by oral inflammatory diseases such as periodontitis play a crucial role in pneumonia pathogenesis.²⁹⁸ Recent animal experiments have demonstrated that P. gingivalis induces pneumonia in mice with periodontitis, significantly increasing levels of cytokines and neutrophils in peripheral blood and lung tissue.²⁹⁹ A recent study innovatively transplanted human oral commensal microbiota into germ-free mice to create human oral microbiota-associated (HOMA) mice; this study analyzed the impact of oral microbiota on lung immunity and systemic conditions during acute lung injury and acute respiratory distress syndrome (ALI/ARDS).³⁰⁰ The results indicated that HOMA mice exhibited systemic dysbiosis; compared to conventional (CNV) mice with sufficient microbial diversity, HOMA mice developed more severe ALI.

Mouthwash is a critical component of oral hygiene, and chlorhexidine mouthwash has been shown to reduce the incidence of respiratory infections; however, long-term use may result in side effects including altered taste, dry mouth, and tooth discoloration. Over the past decade, research has increasingly focused on exploring new mouthwashes derived from natural products. A study comparing a 6.66% clove extract mouthwash with a 0.2% chlorhexidine mouthwash demonstrated that the control group had a 2.06-fold higher risk of developing ventilator-associated pneumonia (VAP) than the intervention group.¹³ Additionally, a triple-blind randomized controlled trial investigating the effects of propolis mouthwash revealed that the intervention group experienced significantly lower incidences of VAP on days 3, 5, and 7 compared to the control group. Propolis mouthwash may represent a viable alternative to chlorhexidine for patients in ICU.³⁰¹