Reviews of Research on the Relationship between Oral Helicobacter pylori and H. pylori Infection

Lingling Zu

Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin China

Reviews of Research on the Relationship between Oral Helicobacter pylori and H. pylori Infection

Lingling Zu

Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin China

oral cavity;Helicobacter pylori; spread;diagnosis

Helicobacter pyloriis one of the most common pathogens among humans, and it is also closely related to stomach diseases. Spread of its diseases must be understood to properly controlH. pylori. OralH. pylorimay also play an important role in the spread of the bacterium. This study provides an overview on the role of oralH. pyloriin spread, diagnosis,and prevention of this organism. The present work also determines difficulties encountered in current studies and progress of research on the relationship between oralH. pyloriand oral diseases.

Helicobacter pyloriis a unipolar, flagellose, spiral-shaped Gram-negative bacterium measuring 0.3–1.0 μm × 2.0–5.0 μm.H. pyloriin epithelial cell surface of gastric mucosa oThen show typical spiral or arc shape and become rod-shaped or spherical in adverse circumstances.H. pyloriis microaerobic,requiring 5% to 8% of environmental oxygen[1]. Humans serve as primary hosts ofH. pylori[2].H. pyloriis also a unique microorganism that can be cultured and isolated from the human stomach[3].

In 1983, Warrenet al.[4]reported that approximately half of gastric ulcer patients feature tiny, curved bacteria atached to their stomach cavity; these bacteria were later cultured and isolated by Marshallet al.[5]. Later studies discovered that this bacterium, that is,H. pylori, causes most of duodenal ulcer and gastric ulcers[6].H. pylorialso primarily results in development of gastric cancer[7]. Discovery ofH. pyloriinfection was considered an important factor that affected people’s health worldwide; however, the manner of its spread among humans remains controversial. In 1989, Krajdenet al.[8]observedH. pyloristrains in membranes of oral plaque organisms and saliva. In recent years, most research focused on whetherH. pylorican settle in the mouth, and whether oral cavity serves as source ofH. pylorispread.

Detection method and detection rate of H. pylori in oral cavity

Using different methods to detectH. pyloriin plaque bio film, saliva, and oral mucosa result in large differences in detection rates[9]. Early research[8]mostly utilized culture method because of harsh survival conditions and presence of other oral bacteria.H. pyloriyields low detection rate. Some scholars[10]used urease test to detect oralH. pyloriand noted high detection rates. However, these experimental methods cannot rule out the presence of other oral urease bacteria,thus causing false positive rates and unclear results. Reliable detection methods include molecular biological tests (such as polymerase chain reaction and gene sequencing), which feature high specificity and sensitivity and are suitable for detection of oralH. pylori.

Molecular biological techniques also present differing detection rates for oralH. pylori. Such findings are atributed to differences in ethnic, dietary, educational, economic conditions[11], and different laboratory tests used by researchers. Although polymerase chain reaction generally presents high sensitivity, it shows strong specificity; primers used also affect detection results. The most commonly used polymerase chain reaction amplification primers includeH. pyloriurease (HPU)-based and cytotoxin-related gene(cag) A-based primers. However, these tests exhibit certain defects as follows: 1) HPU exists in many bacteria, features high homology, and possibly results in false positives when amplified; 2) cagA gene is only expressed in some parts ofH.pyloriand is therefore susceptible to false negative results.Therefore, studies should develop a unified and effective detection method or standard for oralH. pylori.

Oral H. pylori and H. pylori

Correlation between oral H. pylori and H. pylori infection

H. pylorican be detected in the oral cavity; however,studies must still determine the association of oralH.pyloriwithH. pyloriinfection, and whether such conditions are homological. Scholars performed analyses based on two aspects: 1) detection rate of oralH. pyloriinH. pyloriinfectors. Most studies indicated that positive carriers ofH. pylorishow higher detection rates for oralH. pylorithan negative carriers. Recent studies showed close relation ofH.pyloriinfection with oralH. pylori[12–14]. Zouet al.[9]analyzed detection rates of oralH. pyloriamongH. pylori-positive andH. pylori-negative populations. These researchers also observed higher detection rate of oralH. pyloriamong positive carriers than negative carriers [odds ratio (OR) =3.61, 95% confidence interval (CI)=1.91–6.82), confirming the correlation between oralH. pyloriandH. pyloriinfection.These findings also showed that regardless of method used,oralH. pyloriandH. pyloriinfection display correlation. (2)In view of homology of stomach and oralH. pylorigenotype of the same individual, numerous studies showed high homology of oralH. pyloriwithH. pyloriinfection. Caiet al.[15]used polymerase chain reaction to detect genotypes ofH. pyloriand oralH. pyloriin patients with stomach diseases and discovered high homology in the same individual. At 89% probability, the same type ofH. pyloriwas detected in differentin vivoloci[14]. Momtazet al.[16]suggested thatH. pyloriin saliva exhibit homology with strains of gastric specimens and those isolated from feces. Silvaet al.[17]observed high detection rate of oralH. pyloricytotoxic genes inH. pyloriinfectors. This evidence suggests correlation of oralH. pyloriwithH. pyloriinfection. However, these studies still cannot explain whether oralH. pyloricausesH. pyloriinfection, or whetherH. pyloriresults in development of oralH. pylori.

Role of oral cavity in spread of H. pylori

An epidemiological survey[18]showed that human population features high rate ofH. pyloriinfection in crowded living conditions, suggesting thatH. pyloriis possibly spread directly from one person to another. Oral–oral and fecal–oral routes are considered the most possible routes of spread ofH. pylori. AsH. pylorimay also be present in the mouth,oralH. pylorimay also cause infection and spread ofH. pyloriin humans. In this regard, supporters of oral–oral and fecal–oral route theories provide different answers.

Oral–oral theory supporters suggest thatH. pylorican setle in the mouth and spread through media, such as saliva.Mégraud[19]argued that in developed countries, owing to improved hygienic conditions,H. pyloriis unlikely to be spread by feces. Thus,H. pylorimay be spread by oral–oral route. Fernández-Tilapaet al.[20]used polymerase chain reaction and observed high detection rates ofH. pyloriamong positive carriers of serum antibody forH. pylori;this result was possibly caused byH. pylorispread through saliva. For oral–oral theory supporters, ifH. pylorican spread through saliva, then dentists face high risks ofH. pyloriinfection because of their frequent exposure to this medium.However, the current number of infected dentists is low,and such conclusion shows inconsistency. Hondaet al.[21]reported that Japanese dentists face higher risk of infection withH. pylorithan the same-aged control group, and this risk inclines toward young dental practitioners. Losteret al.[22]showed that before clinical practice, dentists do not present higher detection rates ofH. pylorithan dental students.

Supporters of fecal–oral spread theory suggest thatH. pyloriis a passing bacterium in the oral cavity and cannot directly causeH. pyloriinfection. Spread ofH.pyloriin populations may be mediated by drinking water contaminated withH. pylorifrom feces[23]. The main evidence that disprove the theory of fecal spread is low detection rates ofH. pyloriin feces; these values are even lower than those of oral specimens[24]. However, such findings may also be associated with reaction of fecal contaminants in agents of polymerase chain reaction.

To date, some evidence support oral–oral spread or fecal–oral spread, but determining specific route of spread remains improbable. Controversies also surround the assumption of whetherH. pylorican setle and reproduce in the oral cavity for long periods. Scholars[25]suggested that small numbers of oralH. pylorican be detected through polymerase chain reaction, and this finding may be due to low activity of sphericalH. pylori. Thus, oralH. pylorimay not directly lead toH. pyloriinfection.

Role of oral H. pylori in diagnosis of H. pylori infection

OralH. pyloriand its genotype identification and immunological detection may play important roles in identifying types ofH. pyloriinfection and diagnosing types of diseases resulting from the correlation between oralH.pyloriandH. pyloriinfection.

Con firming possible existence of oralH. pylorimay bear significance in identification of varying degrees of gastritis and precancerous lesions. Junet al.[26]observed higher detection rates of oralH. pyloriamong patients with chronic atrophic gastritis than patients with digestibility ulcers and super ficial gastritis. Considering that oralH. pylorifeatures high homology withH. pylori, Tiwariet al.[27]suggested that saliva can be used for reliable noninvasive specimen examination forH. pyloriinfection. Such method analyzes genotypes ofH. pyloricag pathogens, which are isolated from saliva, to assess the type ofH. pyloriinfection among patients.

In addition to direct detection ofH. pylori, detection ofH. pyloriantigens and antibodies in saliva may also provide basis for diagnosis of stomach diseases. Yingyinget al.[28]detected oralH. pyloriantigen on different types of stomach diseases and discovered the association of oralH. pyloriwith degree of gastritis activity and precancerous lesions of gastric mucosa. OralH. pyloriantigen in patients with chronic active gastritis or with moderate to severe intestinal or atypical hyperplasia also present significantly high detection rates.Results showed higher light density ofH. pyloriIgG in the gastric cancer group than chronic atrophic gastritis and gastric ulcer groups. Higher sensitivity was also observed in gastric cancer screened forH. pyloriIgG (72.0%, OD＞0.5),providing a new mode of thinking for primary screening of gastric cancer.

To date, research on the role of oralH. pyloriin diagnosis and identification of gastropathy are still in exploratory stages. One challenge involves clarification of the relationship between oralH. pyloriandH. pyloriinfection and role of oralH. pyloriin development of diseases. Saliva and plaque biofilm can be used as non-invasive specimens ofH. pyloriinfection; these specimens may pose certain prospects in diagnosis of stomach diseases.

Role of eradicating oral H. pylori in prevention of H. pylori infection

Conventional triple therapy is the most commonly used and most effective treatment forH. pylorieradication; it comprises one proton pump inhibitor plus two antibiotics.However, probability of recurrence after treatment is high considering thatH. pyloriexists in the mouth and is swallowed into the stomach along with saliva. Zouet al.[9]observed patients with upper gastrointestinal diseases and who received anti-H. pyloritreatment. Results indicated that despite eradication ofH. pyloriin the stomach,H. pyloristill existed in the mouth; this result may be associated with the presence ofH. pyloriin unique biofilm plaques that were unaffected by medicine.

Considering that oralH. pyloriis a potential cause of recurrence or reinfection ofH. pyloriinfection, some scholars suggested using drugs with periodontal basic therapy to reduce recurrence rate ofH. pyloriinfection.However, experimental results showed inconsistency.Namiotet al.[30]studied the relationship between oral cleaning behavior andH. pylorieradication rate in patients with peptic ulcer after triple antibacterial treatment and observed that habit of maintaining cleanliness of oral cavity(such as brushing of teeth every day, cleaning dentures after meal, or removing dentures before sleeping every night)poses no effect on eradication rate ofH. pylori, indicating that maintaining cleanliness of oral cavity cannot improve eradication rate ofH. pylori. Presenting different findings,Songet al.[31]discovered significantly higher eradication rate ofH. pyloriin patients with periodontal nonsurgical treatment and who use mouthwash than those without periodontal nonsurgical treatment and do not use mouthwash. These results suggest that eradication rate ofH. pyloriwith drug treatment is associated with patient’s periodontal status and oral hygiene, agreeing with findings of Jiaet al.[32]. Bouzianeet al.[33]analyzed the effects of periodontal treatment on eradication rate ofH. pyloribefore 2012 and noted that periodontal treatment can reduce recurrence rate ofH. pyloriinfection in the stomach. These results should be treated with caution because of small amount of raw data. In short, several studies reported that reduction of oralH. pylorican reduce recurrence rate ofH.pyloriinfection, but significant evidence are still needed to support such conclusion.

Oral H. pylori and oral diseases

Oral H. pylori and periodontal diseases

Patients with periodontal diseases may feature suitable conditions for survival ofH. pyloribecause of the presence of oxidation–reduction potential microenvironment with low-oxygen partial pressure in deep periodontal pockets.Studies showed association of oralH. pyloriwith periodontal diseases. For example, Liet al.[34]observed high detection rates for oralH. pyloriin patients with periodontal diseases,whereas the study of Silvaet al.[35]supported the above results. Differently, Silvaet al. were unable to detectH. pyloriin subgingival plaque.

Oral H. pylori and oral ulcer

Oral mucosa and gastric mucosa are all gastrointestinal mucosa and derive from the ectoderm; they present similar development and structure.H. pyloriis one of the causes of gastric ulcer; thus, studies should explore whether oralH. pyloriis associated with oral ulcer. Riggioet al.[36]and Richteret al.[37]discovered the relationship ofH. pyloriwith recurrent aphthous ulcer. Considering that these early studies focused on urease A gene-based primers, detection results showed high false positive rates. Minhaiet al.[38]further used nested polymerase chain reaction with high specificity and sensitivity to detectH. pyloriand observed absence of correlation betweenH. pyloriand recurrent aphthous ulcer. Thus, pathogenesis of oral ulcer from oralH.pyloriinfection requires further explanation.

A small number of studies centered on the correlation between oralH. pylori, caries[39,40], lichen planus[41], and bad breath[42]. However, to date, controversies still surround oralH. pylori, caries, periodontal disease, and recurrent aphthous ulcer. Further research should determine biological mechanism ofH. pylori.

Summaries

Different detection rates ofH. pyloriwere observed in the oral cavity; these results may be related to imperfection of detection methods. Therefore, a unified detection method forH. pylorimust be developed for its accurate detection. A large number of studies showed correlation of oralH. pyloriwithH. pyloriinfection. However, their causal relationship requires additional research. OralH. pylorimay act as“repository” to cause oral–oral spread ofH. pyloriamong populations and infection and recurrence ofH. pylori.Further studies on colonization conditions ofH. pyloriin oral cavity and its relationship with other oral microbes also aid in verifying this theory, providing a new mode of thinking regarding diagnosis and prevention of gastric diseases. OralH. pyloriand periodontal and other oral diseases may also possess a certain correlation. In-depth studies on oralH. pyloriwill aid in prevention and control ofH. pyloriinfection.

Declarations

Acknowledgements

No.

Competing interests

The author declares that she has no competing interest.

Authors’ contributions

LL Zu made the literature analysis and wrote, discussed and revised the manuscript of this review.

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CorrespondenceLingling Zu,E-mail: llzutjmu@sina.com

10.1515/ii-2017-0121