Wang XM, Yee JKC (2016) Is Urea Breath Test a Gold Standard for Diagnosis of H. pylori Infection?. Ann Clin Cytol Pathol 2(1): 1018.

The urea breath test UBT C13,14 is a good rapid diagnostic procedure used to identify stomach infections by H. pylori. It is based upon the ability of H. pylori to convert urea to ammonia and carbon dioxide. Urea breath tests are recommended in leading society guidelines as a preferred non-invasive choice for detecting H. pylori of stomach before and after treatment with diagnostic efficacy at 96.7% sensitivity and 96.2% specificity. However UBT is not a test for detection H. pylori in the mouth. We found that UBT C13 can’t detecting H. pylori in oral cavity such as a person has dysfunction of color blind that can’t see well for certain color. In medical practice, patients with negative results in UBT C13 suggest that their stomach infection of H. pylori is cured. In fact, patients can present negative UBT results and yet exhibit H. pylori infection due to oral infection. The clinical study provides evidence that H. pylori oral infection is nonetheless present. In Asia, more than 20-30 % of the population suffered from oral H. pylori infection but had negative UBT results [1]. This study also showed that oral antigen screening test (HPS) could identify individuals who have no risk for H. pylori gastric but oral infection. It further identified persons with no symptoms but with antigenic evidence of possible oral H. pylori infection who are thus at risk for developing gastric disease. This information was not provided by UBT methods.

The principle of UBT test; patients swallow urea labeled with an uncommon isotope, either radioactive carbon-14 or nonradioactive carbon-13. In the subsequent 10–30 minutes, the detection of isotope-labelled carbon dioxide in exhaled breath indicates that the urea was split; this indicates that urease (the enzyme that H. pylori uses to metabolize urea) is present in the stomach, and hence that H. pylori bacteria are present. In UBT test, since the urea labeled is not dissolved in the mouth, so there were no isotope-labeled carbon dioxide in exhaled breath that is why UBT can’t provide information of H. pylori in the oral cavity. Secondly, the principle of UBT test based on the theory of stomach harbors H. pylori instead oral cavity. Over the past twenty years, the existence of oral H. pylori infection has been controversial, without a definite conclusion. It was proposed that no living H. pylori exists in the oral cavity and that the positive results detected by PCR from oral samples indicate that the presence of H. pylori fragments, rather than living bacteria, or are due to reflux from the stomach, which is infected with H. pylori could not be cultivated from PCR-positive samples. The H. pylori originating from stomach reflux was thought to survive in the oral cavity for only a few hours because of the high oxygen concentration of the mouth. If the above-proposed idea is correct, then the fragmented or dead H. pylori should not have any negative effect on the drug eradication of H. pylori infections of the stomach [1,2]. However, the proposed idea contradicts with PCR studies [3,4] the fact of oral hypoxia environment [5,6] eradication can’t eliminate Oral H. pylori infection [7,8] H. pylori can be cultured in the oral cavity [9], the same original source of Oral and Stomach H. pylori [10,11]. Lower rate of eradication on stomach H. pylori when oral H. pylori positive [12] and Meta analysis [13,14].

Therefore, we proposal a new view that indicated H. pylori colonization of the oral cavity. Before we discussion on H. pylori colonization of the oral cavity, I like introduce H. pylori antigen test for oral urease (HPS) technology that can detecting H. pylori of the oral cavity first.

HPS Technology

HPS (H. pylori antigen test for oral urease): It was specifically detected in saliva using a lateral flow immunochromatographic test device. The device for H. pylori antigen detection in saliva was identical to the device used for oral urease detection in which has same principle of UBT. The HPS test for saliva employed monoclonal antibody that was developed against oral urease. Test Procedure: No food or drink was allowed one hour prior to the test. A swab was put under the tongue for at least one minute. The swab was swirled vigorously for 15 seconds in a buffer solution, and then we expunged as much liquid as possible from the swab by pressing and rotating the fiber portion against the wall of the tube. Two to three drops of saliva/buffer mixture were added into the sample well. As the test kit begins to work, one will see a purple color move across the result window in the center of the test disk. The presence of two color bands (‘T’ band and ‘C’ band) within the result window indicates a positive result. The presence of only one purple color band indicates a negative result. Specificity: An in-house study was conducted with three separate lots of the HPS test to determine its specificity. The following common oral bacteria had been applied: Actinomyces naeslundii, Actinomyces odontolyticus, Bifidobacterium dentium, Corynebacterium matruchotii, Gemella haemolysans, Granulicatella adiacens, Streptococcus gordonii, S. salivarius, S. sanguinis, and Veillonella parvula. All of the above were analyzed and did not show interference or cross-reactivity with the test. Sensitivity: The test’s sensitivity was 10 mg/ml HPS antigen[15]. Our studies show that in 20-25% of UBT negative individual have positive of HPS test that indicated H. pylori exists in oral cavity when stomach no infection [9,15].

Because the majority of physicians and scientists in this field ignore the colonized cavities of H. pylori, approximately 20-30 % of the population of Asia suffers from oral H. pylori infection. In China alone, more than 280 million people carry oral H. pylori, which results in 28 million recurrences of stomach H. pylori infection and the abuse of antibiotics by overuse [16].The massive antibiotic pollution that appears in food, water, and children’s urine has become a serious concern worldwide [17]. Antibiotic abuse kills 80,000 Chinese people every year and leads to extra medical spending of 11.7 billion dollars across the country, which could become a global problem.

Drug regimen is not effective for eliminating oral H. pylori

Drug treatment on stomach H. pylori infection has no effective in H. pylori infection of oral cavity. H. pylori exist in between the teeth and gums called “bio- film membrane” (Bifilm), also known as plaque barrier. It is resistance when the drug into this area. This is why conventional treatment for H. pylori eradication H. pylori infection, but is not efficacy of oral H. pylori in dental plaque. Miyabayashi etc. [12] found the eradication success rate was significantly lower in the oral H. pylori-positive cases (12/23, 52.1%) than in the negative cases (22/24, 91.6%) at 4 weeks after the therapy (p= 0028). Two years later, only 16 of the 23 (69.5%) oral H. pylori-positive cases were disease-free, as compared to 23 of the 24 (95.8%) oral H. pylori-negative cases (p =018). They concluded H. pylori in the oral cavity affected the outcome of eradication therapy and was associated with a recurrence of gastric infection and recommend that oral H. pylori should be examined by nested PCR and, if positive, should be considered a causal factor in refractory or recurrent cases. Our study show the efficacy rate of treatment on stomach H. pylori infection at 82.26% for patients received treatment of mouthwash combined with drug eradication; but only at 61.33% efficacy when patients received drug eradication on stomach. So treatment of oral cavity H. pylori raise about 20% efficacy when combined treatments of both mouth and stomach [10].

Non-antibiotic Formula

There is non-antibiotic treatment for oral H. pylori infection available. Our studies indicated e-polylysine (L) and the Glycerol Monolaurate (GM) used in mouth washing solution. The L is typically produced as a homo-polypeptide of approximately 25–30 L-lysine residues. The epsilon (e) refers to the linkage of the lysine molecules. In contrast to a normal peptide bond that is linked by an alpha carbon group, the lysine amino acids are molecularly linked by the epsilon amino group and the carboxyl group. L belongs to the group of cationic polymers. In water, L contains a positively charged hydrophilic amino group. It is adsorbed electro statically to the cell surface of the bacteria, followed by a stripping of the outer membrane. This eventually leads to the abnormal distribution of the cytoplasm, causing damage to the H. pylori cell. GM is the mono-ester formed from glycerol and lauric acid. H. pylori is extremely sensitive to GM, however there are no reports of L or GM killing H. pylori in vivo. Since both have had a safe record in the food industry, we use L-GM successfully eliminate H. pylori of oral cavity within 2 to 3 months (Figure 1).

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