Journal of Dr. NTR University of Health Sciences

: 2015  |  Volume : 4  |  Issue : 4  |  Page : 203--208

Helicobacter pylori and its orodental implications: A review

Sri Lalitha Kaja1, Kiran Kumar Kattappagari1, Raviteja Chitturi1, Lingamaneni Prashanth2, Baddam Venkata Ramana Reddy1,  
1 Department of Oral Pathology and Microbiology, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
2 NRI Academy of Medical Sciences, Chinakakani, Guntur, Andhra Pradesh, India

Correspondence Address:
Sri Lalitha Kaja
Department of Oral Pathology and Microbiology, Sibar Institute of Dental Sciences, Takkellapadu, Guntur - 522 509, Andhra Pradesh


Helicobacter pylori (H. pylori) is a Gram-negative, microaerophillic, spiral bacterium. The prevalence of H. pylori infection was estimated to range from 40% to 80% and it varies widely. The advancement of biochemical techniques provided new information about the pathogenicity and virulence factors of H. pylori indicating a complex interaction of bacterial and host factors for infection by H. pylori. It is regarded as a serious and transmissible infectious disease linked to duodenal and gastric ulcers, gastric carcinoma, and also as a cofactor in the recurrence of aphthous ulceration. This article focuses on the pathogenesis, disease associations, and the orodental implications of H. pylori.

How to cite this article:
Kaja SL, Kattappagari KK, Chitturi R, Prashanth L, Reddy BV. Helicobacter pylori and its orodental implications: A review.J NTR Univ Health Sci 2015;4:203-208

How to cite this URL:
Kaja SL, Kattappagari KK, Chitturi R, Prashanth L, Reddy BV. Helicobacter pylori and its orodental implications: A review. J NTR Univ Health Sci [serial online] 2015 [cited 2021 Jan 15 ];4:203-208
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Helicobacter pylori (H. pylori) was introduced to the scientific community by Berry Marshall and Robin Warren almost two decades ago; ever since, it has been the focus of biochemical and clinical researches. [1] It was initially named as Campylobacter pyloidis and then C. pylori. It is a spiral, microaerophillic, Gram-negative bacterium that can inhabit various areas of the stomach, particularly the antrum. [2] Nevertheless, H. pylori infection was detected in other sites recently. It was found in the dental plaque, saliva, and also in oropharyngeal lymphatic tissue. Infection with this organism is now being regarded as a serious and transmissible infectious disease linked to duodenal and gastric ulcers, gastric carcinoma, and also as a cofactor in the recurrence of aphthous ulceration, particularly in patients sensitized through gastric colonization and mucosal attachment. [3]


The estimated prevalence of H. pylori infection was found to be in the range of 40% to 80% and it varies widely with geographic area, age, ethinicity, race and socioeconomic status. In general, the prevalence of the infection increases with age and correlates positively with a low socioeconomic status. But in developed nations, infection with H. pylori is declining. [4] Though H .pylori is contagious, its exact route of transmission is not known - it could be either by the oral-oral route or fecal-oral route. Some studies have indicated a role of the gastro-oral route of transmission. [5] The role played by other factors such as ABO blood group, alcohol, tobacco use, nutritional influences, and genetic predisposition to infection has been studied but the results were found to be inconsistent. [6] In a majority of the cases, the infection is asymptomatic and manifests clinically in only 10-15% of the infected individuals. This could be attributed to the virulence patterns of H. pylori and different host immune response.

 Pathogenesis and Virulence Factors

The advancement of biochemical techniques provided new information about the pathogenicity and virulence factors of H. pylori, indicating that its infection requires a complex interaction of bacterial factors and host factors. Several bacterial proteins such as flagellin, encoded by the genes flaA and flaB, are necessary for colonization of the gastric mucosa and are also essential for the transport of the organism to the mucosal surface. [2]

It is able to survive the acidic environment by producing urease, which metabolizes urea to carbon dioxide and ammonia to buffer the gastric acid. Then, adherence occurs via interaction between cell surface glycolipids and adhesins, which are specific to H. pylori and also produces proteins called cecropins, which inhibit the growth of competing organisms. Enzymes such as P type adenosine triphosphatase helps in preventing excessive alkalization of the microenvironment by urease. [7]

Once attached to the gastric mucosa, H. pylori causes injury to the tissue by a complex cascade of events, which depend on both the organism and the host. By means of the cell wall polysaccharide, it disrupts the mucosal integrity. It also releases several pathogenic proteins that induce cell injury. Cytotoxic-associated gene A (CagA) protein, which is produced by CagA is highly immunogenic and may be associated with more severe clinical manifestations such as duodenal ulcer and gastric adenocarcinoma. In addition, protein products of vacuolating cytotoxin gene A (VacA) and the A gene (iceA) produced by contact with epithelium are known to be associated with mucosal injury. [6]

Upon colonization of the gastric mucosa, an inflammatory reaction is induced by the immunogenic properties of H. pylori, which ultimately result in clinical manifestations of the infection. It is mediated by host factors such as interleukins (ILs) IL-1, IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-γ (TNF-γ), interferon-γ (IFN-γ), B-lymphocytes, T-lymphocytes, and phagocytes, which further release reactive oxygen species (ROS) and inflammatory cytokines. H. pylori additionally increases the rate of mucosal programmed cell death. [8]

 Effects on Gastric Physiology

Apart from producing local injury to the gastric mucosa, H. pylori alters the normal gastric secretion. It was shown that H. pylori patients with duodenal ulcers have an increased serum level of gastrin that in turn leads to increased acid output. [9] But patients with gastric adenocarcinoma tend to have pangastritis with involvement of acid secreting body and antrum of the stomach that eventually results in achlorhydria due to the atrophy of parietal cells and cells that produce gastrin. [10]

 Clinical Aspects

Though colonization with H. pylori is not a disease in itself, it is a condition that has a relative risk of developing various clinical disorders of the upper gastrointestinal tract. Histologic gastritis is induced by gastric colonization with H. pylori in all infected individuals but only a minority develops apparent clinical signs. The typical course of the disease in infected patients begins with chronic superficial gastritis that progresses to atrophic gastritis and this appears to be a key event in the cellular cascade that results in the development of gastric carcinoma. H. pylori is also implicated in peptic ulcer disease, nonulcer dyspepsia, and gastroesophageal reflex disease (GERD). [11]

 H. Pylori Induced Carcinogenesis

The International Agency for Research on Cancer (IARC) declared H. pylori as type I carcinogen in 1994. [12] Three supposed pathways of H. pylori carcinogenic action are; [13]

H. pylori can act as a direct mutagen through interaction of intracellular signaling molecules and CagA, which predispose the cells to accumulate multiple genetic and epigenetic changes that promote multistep carcinogenesis.H. pylori-induced VacA can cause immunosuppression by blocking the proliferation of T-cells.H. pylori can induce cell proliferation by increasing the levels of several cytokines and regulatory molecules involved in tumor formation and cell transformation.

In addition to its association with the development of gastric adenocarcinoma, H. pylori is associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphomas by stimulating the lymphocytic infiltration of the mucosal stroma that acts as a focus for cellular alteration and proliferation. [11]

 Association with Other Diseases

Investigators have postulated a relationship between cardiovascular disease and H. pylori infection. But more research is needed before a causal relationship is established. [6] It was proposed that gastritis caused by H. pylori could result in hypochlorhydria or achlorhydria and malabsorption of vitamin B12. [14]

 Dental Implications of H. Pylori

H. pylori in dental plaque

It was implied that patients with chronic gastritis have an increased prevalence of H. pylori in dental plaque. It has been detected in the saliva, supragingival plaque and subgingival plaque which suggest that they may act as reservoirs for H. pylori and could help in reinfection of the stomach. [15] Assumpcao et al. detected H. pylori in 96% of gastric mucosa samples and 72% of dental plaque samples and they exhibited identical vacA and CagA genotypes suggesting a correlation of gastric infection with the presence of H. pylori in the mouth. [16] Oshowo et al. observed that H. pylori was detected in the dental plaque of 15 out of 116 patients who had the presence of the organism in the stomach and demonstrated that in 13 out of 15 patients, the strains were identical in the mouth and stomach, implicating that oral colonization was a rare event but it did occur. [17] Song et al. suggested that H. pylori may belong to normal oral flora as a commensal to the host but in very low numbers such that their identification is difficult. [18] Dental plaque is a biofilm with coexistence of different bacterial species through specific interactions between them and the survival of H. pylori in dental plaque also depends on its ability to interact with other bacterial species. [19] Miyabayashi et al. analyzed the correlation between the success of gastric eradication and prevalence of H. pylori in oral cavity by nested polymerase chain reaction (PCR) before and after eradication therapy. Only 12 (52%) of the 23 patients who were tested positive for oral H. pylori had gastric H. pylori completely eradicated. Seven of these 12 cases remained oral positive and 5 were oral negative and 2 of the oral positive cases showed relapse within 2 years of initial therapy. It implies that presence of oral H. pylori could be an important marker for potentially recurrent or refractory gastritis occurring due to H. pylori infection. [20] Song et al. have shown a variation in the prevalence of H. pylori depending on the location of supragingival plaque samples. H. pylori was detected with the prevalence of 82% among molars, 64% among premolars, and 59% among incisors. [21] This distribution might be due to decrease in the exposure to oxygen gradually from the incisors to the molars, which would favor the growth of H. pylori in the molar area. It was reported that effective elimination of H. pylori from the dental plaque could be achieved by local dental measures and the addition of triple antibiotic therapy did not pose any advantage over local dental hygiene. [22]

H. pylori and periodontal disease

It was proposed that oral health status and different gingival clinical conditions might have an effect on the presence of H. pylori in oral biofilms and this could have an influence on the process of H. pylori gastric infection or reinfection. [23] Several studies have evaluated the prevalence of H. pylori and periodontal diseases but conflicting results can be observed in the literature, which can be attributed to the diversity of the studied population; the specificity of the methods used for the detection of H. pylori. Riggio et al. found that subgingival plaque of 38% of periodontitis patients with no symptoms of gastritis or peptic ulcer were positive for H. pylori and it was concluded that subgingival plaque in individuals with periodontitis could serve as a reservoir for H. pylori. [24] Umeda et al. showed that 40% of the patients with history of gastritis or peptic ulcer had periodontal pockets of greater than 4 mm. [25] There might be a positive link between H. pylori-associated gastric infection and periodontal diseases and they may facilitate transmission and colonization of the bacteria in the gastrointestinal tract. Periodontitis microenvironmental conditions could also be favorable for H. pylori multiplication and could lead to gastric infection. [23]

H. pylori and aphthous ulcers

Gastric ulcers and oral aphthous ulcers bear similarities histologically and as aphthous ulcer often responds to a broad spectrum of antibiotics such as tetracycline, it is assumed that H. pylori could play a role in the development of recurrent aphthous ulcers. [3] Birek et al. determined the frequency of detecting H. pylori DNA in oral samples from recurrent aphthous ulcers and found that 71.9% of recurrent aphthous ulcers samples exhibited H. pylori DNA. Though the causes of recurrent aphthous ulcers are complex encompassing genetic, environmental, hormonal, infectious and immunologic factors, a causal relationship has been postulated between H. pylori and recurrent aphthous ulcers. They also proposed that adherence of the bacterium to oral mucosa and subsequent production of autoantibodies to the epitopes shared by oral epithelial cells and H. pylori might result in tissue destruction associated with aphthous ulcers. Due to similarities in the inflammatory process associated with H. pylori-induced gastritis and recurrent aphthous ulcers, it was proposed that H. pylori might be a cofactor in the pathogenesis of recurrent aphthous ulcers, particularly in people sensitized with gastric colonization and mucosal attachment. [26] Tas et al. conducted a study for evaluating the impact of H. pylori eradication on the clinical course of recurrent aphthous ulcers and found that 30 out of 46 patients with aphthous ulcers were positive for H. pylori and they received eradication therapy. Three months after the therapy, 18 out of 30 patients were negative for H. pylori and 12 were positive. It was observed that the mean number of aphthous ulcers in the H. pylori eradicated group significantly decreased and it provides evidence to support that H. pylori eradication could provide a beneficial effect on patients with recurrent aphthous ulcers. [27]

H. pylori and halitosis

Many studies have detected the presence of H. pylori in the oral cavity of patients with gingivitis and chronic periodontitis, and concluded that the oral cavity may act as a reservoir for transmission of H. pylori. Several studies have investigated the relation of H. pylori infection and halitosis. It was shown that H. pylori was able to produce volatile sulfur compounds such as hydrogen sulfide and methyl mercaptan within the oral cavity suggesting that H. pylori can contribute to the development of halitosis. It is possible that volatile sulfur compounds formed by H. pylori in the stomach are transported through the wall of the stomach into the blood and then via the lungs into the breath as alveolar components. Thus, mouth breath could demonstrate volatile sulfur compounds. [28]

H. pylori and autoimmune diseases

Dysregulation of the immune system resulting in a loss of tolerance to self-antigen characterizes the autoimmune diseases. Numerous environmental agents have been implicated as possible pathogens in the development of autoimmune diseases in susceptible individuals. Chronic infection with H. pylori could serve as a source of persistent antigenic stimulation and induce a systemic inflammatory response. The prolonged interaction of the bacterium with host immune mechanisms makes it a plausible infectious agent for triggering autoimmunity. The antigens of H. pylori were found to activate cross-reactive T-cells, which may lead to autoimmune gastritis and also autoantibodies such as antiphosphotidyl choline antibodies, immunoglobin M (IgM) rheumatoid factor, and single-stranded anti-DNA antibodies produced by B cells. H. pylori was implicated in the pathogenesis of lupus erythematosus, Sjogren's symdrome, and idiopathic thrombocytopenic purpura. [29] A possible role of heat shock protein 60 (HSP60) produced by H. pylori has been implicated in the pathogenesis of Sjogren's syndrome and it has been demonstrated that 79.4% and 88.2% of the patients with Sjogren's syndrome had antibodies against H. pylori and HSP60, respectively. [30] Yamanishi et al. found that B cell-stimulated urease was indeed capable of inducing systemic lupus erythematosus-related autoantibodies in mice, namely anti-ssDNA. [31] It was proposed that H. pylori Cag protein may act as an antigenic stimulus for the production of antiplatelet antibodies. [32]

H. pylori and oral cancer

H. pylori's ability to modify the host immune response and the resultant gastric tumor pathogenesis has been well-documented. [12]],[[13]],[[14] H. pylori is supposed to act in the same way even in the progression of oral and oropharyngeal carcinomas. The interaction of oral H. pylori infection with tobacco or alcohol use or both to increase the risk of squamous cell carcinomas of the head and neck was unclear. Fernando et al. found a significantly higher proportion of H. pylori among betel chewers compared with nonbetel chewers but not among oral cancer patients compared with patients without oral cancer and suggested that betel-chewing may predispose to colonization with H. pylori in the digestive tract through betel-chewing or by swallowing the quid. [33] Dayama et al. suggested a possible association of H. pylori with an increased risk of oral cancer. [34] It has been shown that H. pylori in the stomach correlated with gastric premalignancies and similarly the presence of H. pylori in dental plaque and in the periodontal pathology might influence oral premalignancies. If so, the role of H. pylori as a compounding or contributing factor in oral cancer has to be ruled out. [35]

 Detection of H. Pylori

H . pylori can be detected using rapid urease test or the campylobacter-like organism test, which confirms the presence of H. pylori based on its production of large amounts of urease. H. pylori is the only urease positive bacterium known to reside in the stomach and hence, provides a suitable detection method for use on gastric samples. Several urease-producing species such as Streptococcus, Haemophilus, and Actinomyces reside in the oral cavity and it would be inappropriate to conclude the presence of H. pylori in the dental plaque by positive urease test. Microscopic examination reveals Gram-negative bacteria, curved or spiral rods. The gold standard for the diagnosis of H. pylori is culture, which provides a definitive method for their detection. But the fastidious nature of H. pylori necessitates microaerophilic environment, supplement media, and incubation for up to 7 days. [36] Molecular techniques such as polymerase chain reaction (PCR) permit the amplification of a species-specific region of DNA for subsequent detection by means of agarose gel electrophoresis. Sensitivity and specificity can be increased by the use of a nested PCR. [37] Serological tests to detect the presence of immunoglobin G (IgG) antibodies to H. pylori can be done by use of biochemical assays. Stool antigen testing, a relatively new methodology, uses an enzyme immunoassay to detect the presence of H. pylori in stool specimens. [6]


Triple therapy consisting of 30 mg of proton pump inhibitor, 1 g of amoxicillin and 500 mg of clarithromycin twice daily for 1-2 weeks has been successfully used to eradicate gastric H. pylori and is often recommended as the first line of treatment recommended. [38] In cases with oral infection, full mouth disinfection combined with mechanical antibacterial therapy (scaling and root planning) and antiseptic regimen (chlorhexidine) need to be provided. [23]


The microaerophilic environment of dental plaque and saliva can harbor H. pylori. Prophylactic methods should be practiced to avoid oral carriage of H. pylori. Though many studies have been performed, the true correlation of the presence of H. pylori in the oral cavity and periodontitis or ulcerative disease remains unclear. Further research is essential to confirm its association.

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Conflicts of interest

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