Periodontitis and respiratory infections – exploring the oral–systemic link

Abstract

Periodontitis is a chronic inflammatory disorder that has been recognized as a significant public health concern worldwide. An imbalance between the protective oral microbiota and numerous oral pathogens has been implicated in its pathogenesis. Periodontitis not only impacts an individual’s oral health but also has systemic implications. The pathogenesis of periodontitis and these respiratory infections has been shown to be intricately linked. Numerous clinical research and animal studies have highlighted that the oral health of a population is closely related to their systemic health. It has been suggested that the periodontal pockets can act as a reservoir for oral pathogens, which can later migrate into the respiratory tract through aspiration or systemic circulation. This is a narrative review conducted after a wide literature search on databases such as PubMed, Cochrane, and Google Scholar with keywords including “Periodontitis,” “Respiratory,” “Infections,” “Tuberculosis,” ‘COVID-19’, “Pneumonia,” “Asthma,” and “COPD” published in the last 15 years. The cornerstone of this comprehensive review lies in deciphering the pathogenesis and epidemiology of periodontitis and how these periodontal bacteria contribute to respiratory infections through numerous biological mechanisms, inflammatory pathways, and the potential pathways of infection transmission. We also explore the empirical evidence through research studies supporting the periodontitis–respiratory infections link and also studies with conflicting or inconclusive results. By connecting the dots between this crucial oral–systemic link, we hope to uncover the gaps in the current research and find new avenues for developing cost-effective, targeted, transformative preventive and therapeutic strategies that will not only improve oral health but will also support respiratory health and help reduce the global burden of respiratory infections. Strengthening oral hygiene programs could reduce the burden of respiratory diseases, particularly in elderly and high-risk populations.

Introduction

Periodontitis is a chronic inflammatory disease that affects the supporting structures of the teeth, including the gums and alveolar bone, leading to progressive tissue destruction and eventual tooth loss. It is primarily caused by pathogenic bacteria residing in dental plaque, which initiate a cascade of immune responses and inflammation ^[1]. Poor oral hygiene is a major contributor to the development of periodontitis, along with other risk factors such as smoking, alcohol consumption, obesity, diabetes, and genetic predisposition^[2]. Periodontitis is highly prevalent and affects approximately 11% of the global population^[3]. Beyond its impact on oral health, recent research has increasingly highlighted its association with systemic conditions, including cardiovascular diseases and respiratory infections^[4].

Respiratory tract infections, particularly pneumonia, chronic obstructive pulmonary disease (COPD), and asthma, are major causes of morbidity and mortality worldwide. These infections are primarily caused by pathogens such as bacteria, viruses, and fungi. Emerging evidence suggests that poor oral hygiene and periodontitis may contribute to the risk of respiratory infections, especially in vulnerable populations^[5]. Individuals with periodontitis are at an increased risk of aspirating pathogenic bacteria from the oral cavity into the lungs, which could result in new infections or exacerbate existing respiratory conditions^[6].

Several studies have identified a link between periodontitis and respiratory infections, suggesting that bacteria residing in the oral mucosa play a key role in the development or worsening of respiratory diseases. Furthermore, the chronic low-grade inflammation characteristic of periodontitis may exacerbate other systemic inflammatory conditions such as diabetes. Conversely, chronic systemic diseases like diabetes can worsen periodontal inflammation, creating a bidirectional relationship^[2]. However, the exact underlying mechanisms linking periodontitis to respiratory diseases remain unclear and require further investigation. Understanding this association, particularly in at-risk populations, is crucial for recognizing the broader impact of oral health on systemic health and highlights the potential benefits of integrating oral healthcare practices into the management of chronic diseases to improve overall patient outcomes^[7].

This manuscript was prepared in accordance with the TITAN Guidelines 2025 governing AI use in scholarly publications^[8].

Methodology

This comprehensive review was undertaken to combine the existing evidence that links periodontitis and respiratory infections. Although not conducted as a systematic review, we adopted a structured approach to maintain transparency and methodological rigor.

A wide literature search was performed on databases such as PubMed, Cochrane, and Google Scholar with keywords including “Periodontitis,” “Respiratory,” “Infections,” “Tuberculosis,” “COVID-19,” “Pneumonia,” “Asthma,” and “COPD.” The search was limited to studies in the English language published in the last 15 years. This time period was selected as there was an increased global awareness of respiratory diseases and health and to include the latest 2017 classification of periodontal disease. We also manually screened the reference lists of important articles. Clinical guidelines for periodontal disease and respiratory infections from the American Academy of Periodontology, World Health Organization (WHO), and Centre for Disease Control were reviewed.

A total of 150 studies were reviewed in detail and were included if they:

• Evaluated if periodontitis and respiratory infections are linked.

• Presented relevant information regarding the oral microbiome, inflammatory pathways, pathways of infection transmission, and their clinical implications.

• Evaluated therapeutic interventions for improved patient outcomes and global health.

Studies were excluded if they lacked full-text access, focused only on localized dental conditions, or did not clearly relate to respiratory outcomes. Both human and animal studies were considered if they offered mechanistic insights.

Findings related to the oral microbiome, inflammatory and infection pathways, and clinical correlations were analyzed and thematically synthesized. While no quantitative meta-analysis was conducted, qualitative synthesis was used to identify patterns, gaps, and inconsistencies. Given the narrative format, some degree of selection bias is acknowledged.

HIGHLIGHTS

• Periodontitis is a chronic inflammatory disease of the gums that can lead to tooth loss.

• Periodontitis has been linked to respiratory tract infections, such as pneumonia, COPD, and COVID-19.

• The oral cavity harbors a variety of bacteria, some of which can be aspirated into the lungs and cause respiratory infections.

• Periodontitis may also worsen respiratory infections by increasing inflammation in the body.

• Good oral hygiene practices, such as brushing and flossing teeth regularly, may help to reduce the risk of respiratory infections.

Periodontitis: a closer look

Periodontitis is defined as an inflammatory condition of the periodontium, which includes the supporting and surrounding structures of the tooth, clinically resulting in the loss of tissue attachment. It is radiologically observed as alveolar bone loss^[9–11]. The 2017 World Workshop described the following criteria to classify a patient as a periodontitis case: “Interdental Clinical Attachment Loss (CAL) is detectable in ≥2 non-adjacent teeth, or buccal or oral CAL ≥3 mm with pocketing >3 mm is detectable in ≥2 teeth”^[12]. The periodontium comprises four structures, namely the gingiva or the gum, the cementum, the alveolar bone, and the periodontal ligament^[13].

The classification of periodontitis has evolved with significant advances in research and better upcoming definitions. In the year 1999, periodontitis was classified into the following: necrotizing periodontitis, aggressive periodontitis, chronic periodontitis, and periodontitis as a manifestation of a systemic illness. Pathophysiologically, periodontitis has been classified as periodontitis, necrotizing periodontitis, and periodontitis as a direct manifestation of a systemic disease^[12]. The newer classification of periodontitis combines staging and grading in Table 1.

Table 1.

Staging and grading of periodontitis^[12]

Staging	Description
Stage 1	Incipient periodontitis
Stage 2	Moderate periodontitis
Stage 3	Periodontitis with potential for additional tooth loss
Stage 4	Advanced periodontitis with extensive tooth loss and potential dentition loss
Grading	Description
Grade A	Slow rate of progression
Grade B	Moderate rate of progression
Grade C	Rapid rate of progression

Periodontitis results from poor oral hygiene and leads to polymicrobial bacterial colonization of the gum tissue. It usually involves anaerobes such as Treponema denticola and Porphyromonas gingivalis^[14,15]. Recently, Cryptobacterium curtum, Solobacterium moorei, Selenomonas sputigena, Filifactor alocis, Treponema lecithinolyticum, Dialister pneumosintes, and Synergistes have been identified^[16].

Several risk factors play a key role in the development of periodontal disease, such as dental plaques, developmental grooves, calculi, cervical enamel projections, and short trunks of teeth^[9]. Ehlers–Danlos syndrome, Down’s syndrome, and palmoplantar keratoderma have also been implicated in periodontitis^[17–19]. Type 1 and Type 2 diabetes mellitus and poor nutrition are also considered risk factors^[20–22]. Smoking is thought to cause immune dysregulation and is involved in the pathogenesis of periodontitis^[21,23]. Some studies have shown that increased stress is also associated with periodontal disease^[22].

The prevalence of periodontal disease across the globe varies widely, with 20–50% of the population affected. Among adolescents, the prevalence of periodontitis ranged from 35 to 70% in developing nations while it declined to 4–34% in developed countries^[24]. Belarus, Norway, and Germany, with 0, 1, and 2% of adolescents, respectively, relatively free of periodontal disease, had the lowest prevalence of all countries^[25].

The prevalence in adults showed a similar trend, with 36–63% of affected adults in developing nations, whereas 14–47% of affected adults in developed nations^[24]. India and China, the two most populous countries in the world, had the majority of affected adults. Belarus also had 100% of adults with periodontal disease, while Germany and Taiwan had a 99% prevalence of adults with periodontal disease^[25]. A similar trend was reflected in the elderly, with 100% of individuals in India, China, and Croatia having periodontal disease^[25].

According to the National Health and Nutrition Examination Surveys (USA), “40.7% of those 65 years and older experienced loss of attachment ≥6 mm and 22.7% showed periodontal pockets ≥5 mm”^[26].

As per a recent study, good oral healthcare habits are related to a reduced risk of periodontitis. In individuals with regular tooth brushing habits, a 34% significantly lower chance of having periodontitis was seen. Individuals who regularly visited dentists, at least once a year, had a 44% lower chance of having periodontitis. It was also noted that interdental cleaning with dental floss offered only a small reduction (around 13%) in the incidence of periodontitis^[27].

The inflammation secondary to periodontitis is associated with numerous systemic conditions such as diabetes mellitus, chronic kidney disease, osteoporosis, erectile dysfunction, dementia, rheumatoid arthritis, cardiovascular disease, cancer, and respiratory diseases^[28]. Several mechanisms have been proposed to explain these associations, including chronic systemic inflammation driven by persistent periodontal infection, translocation of periodontal pathogens into the bloodstream causing bacteremia, and oropharyngeal or digestive translocation of periodontal bacteria; the former causing aspiration pneumonia^[29], whereas the latter causing intestinal dysbiosis and gut-mediated systemic inflammation^[30]. Patients with periodontal disease are also found to have elevated levels of pro-inflammatory mediators (such as interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein, and fibrinogen) and increased neutrophil numbers in the blood^[31]. This low-grade inflammation can contribute to endothelial dysfunction, insulin resistance, and immunomodulation, thereby linking periodontitis to various systemic diseases. There is also a negative correlation of periodontitis with outcomes in pregnancy, with low birth weight, preterm delivery, fetal growth restriction, and preeclampsia being observed^[32].

Respiratory infections – understanding the scope

Respiratory tract infections are primarily categorized into upper and lower respiratory tract infections. Upper respiratory tract infections (URTI) involve the nose, pharynx, and other related structures, and can present as pharyngitis, rhinitis, otitis media, and sinusitis^[33]. Lower respiratory tract infections (LRTI) encompass a wide spectrum of clinical diseases that manifest as bronchitis, bronchiolitis, and pneumonia with clinical or radiological confirmation, although overlap might exist^[34,35]. Pneumonia is an acute form of LRTI where the alveoli fill with fluid, clinically ranging from mild cough and dyspnea to life-threatening sepsis, acute respiratory failure, and acute respiratory distress syndrome^[36,37].

Pneumonia in children can be classified by the WHO Integrated Management of Childhood Illness, which includes pneumonia and severe pneumonia^[38]. Pneumonia in adults can be classified using the confusion, uremia, respiratory rate, blood pressure, and age ≥ 65 (CURB-65) score^[39].

Impact on public health

LRTI is a leading cause of mortality and morbidity globally, exhibiting a bimodal distribution, with higher incidence in both children under 5 years old and the elderly over 70 years old^[40]. A meta-analysis revealed that in 2015, there were 6.8 million hospitalizations globally due to pneumonia, and 1.1 million hospital deaths attributed to this condition^[41]. Although age might be an important risk factor for pneumonia, adults with underlying medical conditions have shown a poorer outcome^[40,42].

Risk factors of respiratory infections

Pneumonia can be either community-acquired or hospital-acquired, and it can spread through the aspiration of a pathogenic microorganism or by inhaling a pathogenic microorganism^[43]. Various microorganisms are implicated, the most common being Streptococcus pneumoniae and influenza virus^[44,45].

A multivariate analysis of the risk of developing severe pneumonia showed the following risk factors in descending order of their severity^[45,46].

• Age > 65 years

• Male gender

• Smoking

• COPD

• Diabetes mellitus

• Congestive cardiac failure

• Use of inhaled medications

• Kidney failure

• Chronic liver disease

• HIV infection

• Dementia.

Ortega et al suggested that improper and inadequate oral hygiene and disorders of swallowing were also associated with pneumonia. Inflammatory mediators like cytokines, which are produced locally in periodontal diseases, are implicated in the pathogenesis of the inflammatory process in pneumonia^[46,47].

Oral–systemic health connection

Various types of publications, including epidemiologic data, clinical research and animal studies, have clearly demonstrated that oral health of the population has a significant effect on their systemic health^[48]. There is hardly any disease or organ system that is not affected by periodontal disorders^[49,50]. In a susceptible individual, the different mechanisms involved in the oral–systemic health connection include genetic predisposition, environmental factors, pharmacotherapy, microbial dysbiosis due to bacteremia and viremia, and disturbances in the host immune response^[48]. In many diseases, a bidirectional or two-way impact is observed. In patients with obesity, diabetes and metabolic syndrome, systemic inflammation is heightened when they have underlying periodontitis^[51]. On the contrary, obesity has been shown to worsen periodontal bone loss^[52]. In asthma and Alzheimer’s disease too, a bidirectional interaction is well known^[53,54].

Periodontitis and respiratory infections

The oral biofilm harbors a plethora of microbes comprising bacteria, viruses, and fungi. The dental microbiota acts as pathogens in susceptible subjects with poor oro-dental hygiene, thereby rendering them to be at a high risk of acquiring or exacerbating pulmonary illnesses^[55–57]. Moreover, the low-grade systemic inflammation that is encountered in patients with periodontal diseases adversely affects the lung functions over a period^[58]. Increased mucus, which is triggered by elevated cytokines and chemokines produced by periodontal inflammation, can lead to exacerbations of respiratory infections^[59].

Pneumonia

Many bacterial pathogens implicated in periodontitis have been cultured from the respiratory secretions of patients with pneumonia, especially the hospital-acquired and ventilator-associated ones. There are conflicting data on the link between periodontitis and community-acquired pneumonia^[60,61]. It is postulated that, by virtue of micro-aspiration, oral biofilms lead to the development and/or worsening of pneumonia in edentulous and elderly subjects^[62]. Since the number of anaerobes outnumber aerobes by a ratio of 1000:1 in the oral flora, the majority of these aspiration pneumonias are anaerobic infections in the form of necrotizing pneumonia, chronic anaerobic pneumonitis, and lung abscess^[63,64].

Tuberculosis

A two-way link between periodontal disease and tuberculosis has also been hypothesized. A high occurrence of periodontitis is found in patients with tuberculosis^[65]. Conversely, the offending organism Mycobacterium tuberculosis was isolated in the saliva and dental plaque scrapings of patients with tuberculosis and periodontitis^[66]. Although the current evidence is limited, the oral microbial changes in TB patients may serve as a model to understand pathogen spillover in respiratory diseases.

Bronchiectasis

Although many studies have depicted the strong correlation between COPD and periodontal infections^[67–70]. There is hardly any research on the impact of periodontitis in patients with bronchiectasis^[71]. A randomized controlled trial (Clinical-Trials.gov Identifier: NCT02514226) is underway to investigate the link between periodontal disease and bronchiectasis^[72]. This study aims to explore the bacterial load, as determined by quantitative PCR, of Pseudomonas aeruginosa, Staphylococcus aureus, and P. gingivalis in the sputum, saliva, and nasal washings of patients with bronchiectasis and periodontal disease. Another study has shown a significant alteration of seven different genes in patients with bronchiectasis having chronic periodontal inflammation^[73].

COVID-19

With the advent of COVID-19, the oral and gingival area has gained importance due to the high SARS-CoV-2 concentration and a sizeable number of angiotensin-converting enzyme-2 (ACE-2) receptors in the oral mucosae^[74,75]. Various bacteria, usually found as commensals in the oral flora, were cultured in the bronchial lavage fluid of patients with COVID-19, especially those who were on ventilatory support^[76–79]. Current evidence shows that the composition of the oropharyngeal microbiome is linked to the severity of COVID-19 manifestations through an inflammatory response involving the interaction between SARS-CoV-2, other microorganisms, and the host immune system^[78]. It has been postulated that such infections are more common in the elderly population, who are at a very high risk of aspiration in view of their edentulous state and impaired swallowing reflex^[80].

Periodontitis–respiratory infections link

Oral pathogens are also implicated in respiratory infections. These oral pathogens are kept in check by the oral microbiome. Periodontitis is a chronic polymicrobial disorder that develops due to an imbalance between these pathogenic microorganisms and the oral microbiota. COPD and periodontitis share associations through their common risk factors^[81]. Dental plaque acts as a reservoir for respiratory pathogens, which are later shed and contaminate the respiratory tree, causing infection^[82]. Good oral health, dental plaque decontamination with chlorhexidine mouthwash, and professional tooth cleaning reduced the occurrence of respiratory diseases in high-risk geriatric patients^[83]. The systematic reviews conducted by Azarpazhooh and Leake showed an association between periodontal disease and asthma, COPD, and pneumonia^[84,85]. This link has been illustrated in Figure 1, emphasizing its pathogenesis and the role various factors play in its development.

Figure 1.

Illustrates the link between periodontitis and respiratory infections^{[81,82,84–86]}.

COPD

Gingival ulceration can cause bacteremia. The association between periodontitis and COPD is suggested by the similarity in disease processes, such as the mass production of inflammatory cytokines and reactive oxygen species by neutrophils in the bloodstream^[87]. Periodontal lesions can induce systemic inflammation, further contributing to COPD^[88]. The most common bacterial species implicated in both COPD and periodontal disease are P. intermedia, Catonella morbi, and Dysgonomas wimpennyi. Good oral hygiene and treatment of periodontal disease will have a positive impact on COPD patients and decrease the frequency of exacerbations^[89–91].

COVID-19

The ACE-2 receptor acts as the initial binding site for SARS-CoV-2. Proteases such as Furin and cathepsin L are released due to the inflammatory process initiated by pathogens in periodontitis. These proteases cleave SARS-CoV-2 glycoproteins and help them to adhere to the ACE-2 receptors. The AAP 2017 classification stages 3 and 4 are characterized by deep periodontal pockets, which in turn show associations with moderate and severe COVID. This suggests a positive correlation between COVID-19 and periodontal disease severity^[92]. The risk and severity of symptoms and outcomes of COVID-19 correlate with the severity of periodontal disease^[93].

Asthma

Due to the use of syrups with a high sugar concentration, corticosteroids, and sedatives that cause reduced saliva secretion in asthma, children have a greater predisposition to dental illnesses^[94]. Data from the systematic review conducted by indicates a significant link between asthma and periodontal disease^[95,96]. The risk of developing bronchial inflammation increases fivefold in those suffering from periodontal diseases. Asthma and periodontitis are directly related^[97].

Pneumonia

Gastric contents or oropharyngeal secretions may be aspirated into the lungs causing aspiration pneumonia. This can be prevented if oral infections are not left untreated, as they may result in the destruction of tooth enamel and other periodontal diseases^[86]. Gram-negative periodontal pathogens colonize within the biofilms of dental plaque, and eventually, if left untreated, the gingivitis can develop into chronic bacteremia. As the pathogens become part of a lung infiltrate, they cause either a unilateral or bilateral lung infection^[98]. Good, consistent oral care and hygiene may prevent post-pneumonia mortality in elderly individuals in hospitals and nursing homes^[99].

Lung abscess

Around 60–80% of organisms causing lung abscesses are anaerobes. These organisms isolated from lung abscesses belong to human oral flora, thus consolidating the connection between the two pathologies^[100]. The most common predisposing factor leading to lung abscess has been found to be poor oral hygiene^[101]. Few examples of such organisms are Porphyromonas endodontalis, Streptococcus constellatus, Tannerella forsythia, Bulleidia extructa, Parvimonas micra, Veillonella, and others^[102–107]. Aspiration pneumonia is one of the most common causes of lung abscess^[108].

According to a recent study, around 61% of patients who were diagnosed with lung abscess were suffering from periodontitis^[109]. However, since majorly, sputum cultures and bronchoalveolar lavage are the primary diagnostic modalities used to isolate the causative organism, the samples are usually contaminated with oral flora^[100]. Percutaneous aspiration biopsy and next-generation sequencing for identifying the organisms causing the lung abscess are newer modalities in play^[110].

Empirical evidence

Numerous research studies have explored the relationship between periodontitis and respiratory infections. A substantial body of evidence supports this link, highlighting the role of oral pathogens in aspiration pneumonia, COPD exacerbations, and COVID-19 severity^[81]. However, some studies present conflicting or inconclusive findings, suggesting that observed associations might be influenced by confounding variables such as smoking, comorbidities, or socioeconomic status^[57,58]. These discrepancies underline the need for cautious interpretation and for conducting well-designed, larger longitudinal studies^[57,58].

An important distinction to note in the evaluation of these studies is between statistical significance and clinical significance. Statistical significance indicates that the observed association is unlikely to be due to chance, often evaluated using P-values (e.g., P < 0.05). Clinical significance, however, reflects whether the effect size has meaningful, practical implications for patient care^[81]. For instance, a study may find a statistically significant decrease in exacerbations among periodontitis patients after treatment, but if the sample size is small, the effect size might be too minor to affect real-world outcomes significantly^[88]. Thus, while statistical tests confirm a relationship, the true health impact (clinical significance) requires broader validation in large, diverse populations. In summary, while empirical evidence points toward a strong oral–systemic link, it is crucial to balance statistical outcomes with clinical relevance and interpret findings considering study design, sample size, and patient demographics.

Research studies supporting the periodontitis–respiratory infections link

Numerous studies, including those during the COVID-19 pandemic, have examined the relationship between periodontitis and respiratory infections. A case-control study on the correlation between COVID-19 and periodontitis^[111] found a significant correlation, where patients with periodontitis were at increased risk of severe COVID-19 outcomes. This establishes the connection between poor oral health and heightened vulnerability to viral respiratory infections. Similarly, a study of the elderly suggested that periodontitis can contribute to severe lung involvement in COVID-19 infection by allowing periodontal bacteria to infect the lungs^[112]. This demonstrates how oral infection pathogens can complicate respiratory infections, particularly in the elderly. Furthermore, research that evaluated maternal oral health during pregnancy established that periodontal disease posed a threat to community-acquired and hospital-acquired respiratory infections^[113], demonstrating the widespread impact of oral disease in healthcare settings and throughout life.

Other studies have validated this connection. A case-control study on the association of periodontitis with nosocomial pneumonia established a direct association between the two conditions^[114], suggesting that periodontal infection might be a factor in the development of hospital-acquired pneumonia. Another study provided an explanation of the role of infections in chronic respiratory conditions, noting that aspiration of high bacterial content oral fluids can transmit pathogens from the oral cavity to the lungs^[115]. This mechanism accounts for how periodontal disease can lead directly to respiratory infection. Saini and Saini^[116] explored the systemic effects of periodontitis and found that periodontitis can trigger the release of pro-inflammatory cytokines, which can compromise the immune response and increase the vulnerability to respiratory disease. In another case-control study, Parashar et al (2018) found that periodontitis reconfigures the oral microenvironment in a manner that facilitates colonization of the mucosa by respiratory bacteria^[117], thus favoring respiratory tract infections through microbial invasion and inflammation.

Another study assessed the periodontal status of disabled students and found a clear correlation between poor oral hygiene and a higher incidence of URTIs^[118]. This finding again emphasizes the importance of promoting oral care among risk groups to prevent avoidable respiratory morbidity. Together, the findings from these studies continually establish a firm link between periodontitis and respiratory infections like COVID-19, pneumonia, and chronic respiratory disease. The findings highlight the need to integrate oral care into respiratory disease prevention strategies. Future research, in turn, should have an emphasis on clarifying the underlying biological mechanisms as well as implementing focused interventions that aim to address the periodontal disease process within a comprehensive approach to improving respiratory health.

Periodontal treatment reduces respiratory infections

Recent studies have indicated that periodontal treatment reduces the risk of respiratory infections. Shen et al (2017) investigated the impact of periodontal treatment on outcomes for respiratory events among adult asthmatic patients. The results indicated that patients who received periodontal treatment were hospitalized less often with respiratory complications, such as severe asthma exacerbations, pneumonia, and respiratory failure, needed far fewer ICU admissions, and died fewer times overall^[119]. The findings suggest that periodontal care may significantly reduce the likelihood of severe respiratory complications in asthma patients, noting the importance of regular oral health screening to overall health care. Shen et al (2016), in another study, evaluated the effects of periodontal treatment on COPD-associated respiratory events. The study showed fewer hospital admissions, emergency department stays, and intensive care unit admissions for respiratory disorders, such as acute exacerbation and pneumonia, among treated individuals. In addition, the treatment group also showed a 37% reduction in mortality risk when compared to the control group^[120], and this indicates that periodic periodontal treatment can reduce respiratory complications and achieve better outcomes in such a risk group.

Limitations of the studies

Small studies with only 20 cases per group generally lack adequate statistical power, which makes it more likely to have false negatives (type II errors). With small sample sizes, study results are typically not generalizable and overstating the variability observed in the groups being studied could happen. These studies are also more prone to bias and their results need to be interpreted with caution. The clinical relevance of the results remains uncertain without further validation using larger trials, as the results may not hold true in the larger population. A study by Flint et al (2019) revealed that smaller sample sizes in neuroimaging research led to overestimated performance metrics, highlighting the risks of misestimation^[121]. Similarly, a meta-analysis by Lin (2018) examined the impact of small sample sizes on meta-analytic results. The study found that sampling errors in small studies can lead to substantial bias in effect size estimates, particularly for standardized mean differences, odds ratios, and risk ratios. Even when individual studies had more than 50 participants, bias was noticeable, emphasizing the need for caution when interpreting findings from small studies in meta-analyses^[122]. These findings underscore the necessity for larger, well-powered studies to obtain reliable and generalizable results in clinical research

Biological mechanisms

Oral microbiota and its composition

As shown in Figure 2, the oral mucosa contains around 700 indigenous kinds of microbes, including fungi, bacteria, and viruses. Disturbance in this oral ecosystem has been implicated in the development of various systemic diseases apart from periodontal diseases^[97,98].

Figure 2.

Illustrates the various microbes and their location in the oral cavity^[123].

Role in the maintenance of oral health

Porphyromonas gingivalis is associated with several forms of periodontitis. P. gingivalis has long fimbriae containing FimA subunit protein, which aids in its pathogenicity and is responsible for most of the inflammatory processes of P. gingivalis^[124].

Nisin is a bactericidal compound where Nisin A acts against Gram-positive bacteria such as Streptococcus species, and Nisin Z is effective against Gram-negative bacteria such as Prevotella, P. gingivalis, and Treponema^[125,126].

Bacterial complexes are classified based on pathogenicity. The red complex is most strongly associated with advanced periodontal disease^[127–131]. Table 2 shows the microbial complexes involved in periodontal disease.

Table 2.

Illustrates the microbial complexes; the various bacteria found in those complexes and their associations with diseases^[127–131]

Complexes	Red complex	Orange complex	Green complex	Yellow complex	Purple complex	References
Bacteria	P. gingivalis, T. denticola	Fusobacterium nucleatum	Capnocytophaga species	Streptococcus sanguinis	Actinomyces odontolyticus	[6.15; 6.16; 6.18 6.19]
		Prevotella intermedia	Aggregatibacter actinomycetemcomitans (specific serotypes)
				Streptococcus mitis
					Veillonella parvula
		Campylobacter rectus
	T. forsythia			Streptococcus oralis
		Peptostreptococcus micros
				Streptococcus gordonii
Association	Strongly associated with advanced periodontitis, bone loss, and deeper periodontal pockets	Known as bridging bacteria	Associated with mild gingival inflammation but can cause more serious infections in immunocompromised individuals	These are among the early colonizers and are usually associated with healthier, nonpathogenic conditions in the oral cavity	They are among the earliest colonizers; these bacteria are usually associated with healthy periodontal and gum tissue	[6.16; 6.17; 6.18; 6.19]
		Act as a bridge between the early colonizers and the more pathogenic red complex

Inflammatory pathways and immune response

T helper 17 pathway

Porphyromonas gingivalis favored the generation of T helper 17 cytokines (IL-6, IL-23) through Nuclear Factor kappa-light-chain-enhancer of activated B cells activation while degrading the Th1-related IL-12 cytokine^[132].

Complement pathways

It is suggested that all three complement pathways are involved in periodontitis. Porphyromonas gingivalis activates Toll-like receptor 2, which in turn activates PI3K and CR3. This releases C5a from C5, which activates the cyclic adenosine monophosphate-dependent phosphokinase A pathway. This leads to an impaired inducible nitric oxide synthase-dependent bacterial destruction^[133].

Neutrophil extracellular traps

An overproduction of neutrophil extracellular traps can cause a disruption in homeostasis and favor periodontitis by protecting harmful bacteria^[134,135].

Potential route of periodontal infections

Currently, it seems likely that saliva and direct mucosal contact are the only transmission routes of periodontal bacteria. Common risk factors include inadequate oral hygiene and systemic diseases^[136].

Mechanisms through which oral bacteria can cause respiratory infections include:

• Aspirating oral pathogens into the lower respiratory tract^[137].

• Periodontitis-associated salivary enzymes can promote mucosal adhesion and colonization of respiratory pathogens^[137].

• Periodontitis may hinder salivary clearance of pathogenic bacteria^[137].

• Cytokines released by the periodontitis disease process aid in respiratory infections and pathogenesis^[137].

Clinical implications

Recent advances in research suggest a noteworthy connection between periodontal disease and respiratory infections, including community-acquired and hospital-acquired pneumonia^[118]. Aspiration of periodontal bacteria like P. gingivalis triggers a cascade of inflammatory reactions from the epithelium of respiratory lining below the pharynx, contributing to the development of pneumonia and exacerbation of COPD^[138]. Poor oral hygiene and a depressed immune system also play a major role in the same^[139]. Treatment for periodontal diseases reduces the risk of pneumonia in specific at-risk populations, as reported in a study^[140]. A recent trial showed that there was a remarkable decrease in the incidence of exacerbations of COPD in patients who had undergone initial periodontal treatment, while the control group had an increase in the median infective exacerbations, i.e., from 2 to 3 during the follow-up period^[88]. Another study showed a link between lung cancer and oral bacteria, specifically, the orange complex bacteria, which damage the periodontal complex and cause disease^[141].

Thus, there is a complex interplay of a person’s comorbidities on the health of their periodontal complex and a good knowledge of the same is of paramount importance to dental as well as medical health professionals.

A knowledge gap exists due to a lack of evidence that indicates that prevention or treatment of periodontitis affects health status and reduces comorbidities that are linked to periodontitis^[142].

A multidisciplinary team involving dentists and other healthcare professionals, including physicians and nurses, should be involved to help in the identification of any possible association between periodontitis and chronic systemic diseases. Hence, people suffering from chronic periodontitis should be screened for an underlying chronic disease. Conversely, people diagnosed with respiratory diseases should take umpteen care of their oral health^[143].

A consensus report of the Joint Workshop by the European Federation of Periodontology and the European arm of the World Organization of Family Doctors (WONCA Europe) suggested better cooperation between dentists and family doctors for early detection and treatment of noncommunicable diseases and periodontitis in dental and family medicine OPD, respectively, thus consolidating the efforts needed to tackle the diseases^[144].

Severe periodontitis causes a significant burden on healthcare, social, and economic systems throughout the world. It is a public health issue and prevalent in lower socioeconomic groups. Not only health professionals, but even governments, multinational companies, and local communities must hold hands and come together to overcome this neglected entity^[145].

Promotion and adoption of basic oral hygiene practices, such as tooth brushing, flossing, and using mouth rinse, should be encouraged, especially in underdeveloped and predisposed populations, as a primary prevention tool. Routine oral checkups and screening for periodontal diseases should also be inculcated in medical practice^[146]. Similarly, anti-smoking campaigns, smoke cessation clinics, and appropriate psychological and social support should be included in tackling the problem^[147]. The vital and integral role played by oral health in the general health and well-being of an individual should be highlighted in the policies made by governments and backed by National Dental Associations^[148].

• At-risk populations (elderly, ventilated, immunocompromised).

• Proven interventions (chlorhexidine rinses, tooth brushing, professional cleanings).

• Interdisciplinary care (GPs, pulmonologists, dentists).

Future directions and research needs

While many case reports, reviews and systematic reviews have been published on the link between periodontitis and respiratory infections, there has been a clear lack of interventional studies on the same subject. Moreover, most of the studies done show an association between the two entities; however, a causal relationship between both is yet to be established. There is also a paucity of research on the outcomes of respiratory diseases following periodontal therapy^[149].

Several different areas of interest and queries need to be explored despite an association seen between periodontitis and respiratory infections. First, if oral bioflora and any change in the oral microenvironment could be used as possible biomarkers to foretell the occurrence of respiratory infections. Second, if changes in the oral microenvironment are adverse in some cases and trigger the onset of infections and diseases, can a favorable environment be created for lung health. Third, identification of biological processes and metabolites involved in the pathway, along with pathogenic factors related to respective periodontal microorganisms and diseases, might help in diagnostic as well as therapeutic purposes in the near future^[150].

Conclusion

Thus, periodontitis can be strongly linked to respiratory tract infections, especially with the increase in lung infections, which have contributed to an increase in morbidity and mortality. This has also emphasized an increased focus on oral hygiene practices and their inclusion in daily medical practices. Moreover, it has now been understood that periodontitis not only causes lower respiratory infections directly but is also associated with other systemic health conditions. It creates a persistent state of inflammation, which is intensified when other chronic diseases come into play. Furthermore, the prevalence of periodontitis is dependent on geographical areas, age groups, and socioeconomic status of the population. Therefore, this field requires further research to help clarify the causality and to establish a solid relationship between periodontitis and respiratory tract infections and to help mitigate the vicious cycle that ensues upon their interaction. Recognizing the oral–respiratory axis opens new avenues for interdisciplinary prevention strategies that are both cost-effective and scalable across populations.

Ethical approval

This study did not involve human participants or animals.

Consent

Not applicable, as no individual patient data were used.

Sources of funding

No external funding was received for this manuscript.

Author contributions

S.S.B. (joint first author) and Y.S.C. (joint first author) contributed equally to the conception and design of the review, extensive literature search, initial drafting of the manuscript, and coordination among all co-authors. K.P. participated in the literature review, manuscript organization, and drafting of key sections related to the oral–systemic interface. A.R. provided senior supervision, critical inputs on clinical relevance, and major revisions of the final draft. A.S.S. contributed to the conceptual framing, academic validation, and refinement of the manuscript’s scientific accuracy. H.V.M. and A.D. assisted in literature compilation, referencing, and content structuring of the review. H.T.J. contributed to the review of public health and epidemiological aspects related to oral and respiratory infections. R.E.A.R.C. offered academic mentorship, critical editing, and oversight of the final scientific content. A.C.C. contributed to the synthesis of regional data, proofreading, and formatting of the final manuscript. C.P. provided expert insight on respiratory diseases, guided manuscript alignment with clinical frameworks, and supervised the medical accuracy of respiratory sections. A.D. (corresponding author) coordinated all stages of manuscript development, performed critical revision and language editing, ensured compliance with journal standards, and approved the final version for submission.

Conflicts of interest disclosure

The authors declare no conflicts of interest related to this work.

Guarantor

Ayush Dwivedi.

Research registration unique identifying number (UIN)

Not applicable.

Provenance and peer review

Not commissioned; externally peer-reviewed.

Data availability statement

Data sharing is not applicable to this article as no new datasets were generated or analyzed during the study. All information is derived from previously published literature and publicly available scientific sources.

Acknowledgements

Not applicable.