Oral H. pylori Infection
- 1. Research Lab of Oral H. pylori, USA
- 2. Beijing University First Hospital, China
Introduction
During the past 25 years, there has been disagreement regarding the existence of H. pylori in the oral infection. It was proposed that no living H. pylori exists in the oral cavity and that the positive results detected by a polymerase chain reaction (PCR) in the oral cavity may be a fragment of H. pylori, instead of living bacteria, as part of a reflux from the stomach: H. pylori could not be cultivated from PCR-positive samples. The H. pylori comes from the stomach reflux only to survive in the oral cavity for a few hours because of the high oxygen concentration in the oral cavity. If the above proposed idea is correct, then the fragment or dead H. pylori should not have any negative effect on the drug eradication of H. pylori infections of the stomach [1-4].
However, the proposed idea contradicts with PCR studies, because there are a number of studies using PCR as the indicated research tool; they indicated PCR is a sensitive and reliable test for detecting oral H. pylori [5].The proposed idea contradict with the fact of oral hypoxia environment, because the subgingival plaque of the oral cavity has microaerophilic environments favorable for the growth of this bacterium, and H. pylori was detected in the supragingival plaque of individuals with H. pylori gastric diseases by a rapid urease test and real-time PCR analysis[4]. The proposed idea contradicts with eradication can’t eliminate oral H. pylori infection, because there are a number of studies that show when patients received drug treatment for stomach H. pylori, the drug did not eliminate oral H. pylori. Also, a study shows that mouth-rinse treatment alone or combined with periodontal treatment can, to some extent, reduce the prevalence of oral H. pylori and improve the eradication rate of gastric H. pylori [6,7]. The proposed idea contradicts with H. pylori can be cultured in the oral cavity. In the PCR-positive saliva sample, can H. pylori be confirmed by culture? The answer is yes! One study showed that H. pylori from a saliva sample can be cultured in individuals with all positive test results (HPS and HPF) of the oral cavity [5].The proposed idea contradicts with the same original source of oral and stomach H. pylori. The remarkable genotype diversity among stomach, saliva, and stool samples showed that more than one H. pylori genotype may exist in the same patient [8]. The proposed idea contradicts with the fact of lower rate of eradication on stomach H. pylori when oral H. Pylori positive. Miyabayashi et al, [9] 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. pyloripositive cases were disease-free, as compared to 23 of the 24 (95.8%) oral H. pylori-negative cases (p =018). The eradication efficiency in the stomach was 85.8% (187/218), while in the oral cavity it was only 5.7% (9/158) (OR = 55.59, P < 0.00001). H. pylori was more difficult to eradicate in the oral cavity than in the stomach, and may be a source of re infection.
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 [5]. The proposed idea contradicts with Meta analysis. A meta-analysis published in 2011 indicated that the prevalence of H. pylori infection in the oral cavities of gastric H. pylori-positive patients was significantly higher than in gastric H. pylori-negative patients (45.0% vs 23.9%). The pooled OR was 3.61 and the 95%CI: was 1.91-6.82 (P < 0.0001). Different diagnostic methods produced different pooled ORs with PCR the highest (OR = 5.11, 95%CI: 2.08-12.54, P = 0.0004) and the rapid urease test the lowest (OR= 2.00, 95%CI: 0.80-5.00, P = 0.14). The 44.8% (91/203) prevalence of H. pylori infection in the oral cavity in patients with clinical and/or histologic gastroesophageal diseases was significantly higher than the 13.2% (21/159) in patients with non-ulcerous dyspepsia or healthy controls (OR = 5.15, 95%CI: 2.97-8.92, P < 0.00001) [10]. The eradication efficiency in the stomach was 85.8% (187/218), while in the oral cavity it was only 5.7% (9/158) (OR = 55.59, P < 0.00001). H. pylori was more difficult to eradicate in the oral cavity than in the stomach, and may be a source of reinfection.
There are several reports indicated non-gut organs have been harbored of H. pylori, such as vagina [11], nasopharyngeal sinus cavities [12], coronary plaque [13], otitis media [14], breast [15]. However, further confirmation study should be follow up.
After review of studies in past 5 years, there are four important facts here we want emphasized in H. pylori colonized in oral cavity;
1. Urea Breath Test (UBT) C [13] is a gold standard for diagnosis of stomach H. pylori, but is not so for detection in the mouth. We found that UBT C [13] has color blind that see H. pylori in the stomach, but can’t detecting H. pylori in oral cavity. In medical practice, patients with negative results in UBT C [13] 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 90% of the population suffered from oral H. pylori infection but had negative UBT results [16]. This study also showed that oral antigen screening test could identify individuals who have no risk for H. pylori gastric 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 [17].
2. Drug treatment on stomach H. pylori infection has no effective in H. pylori infection of oral cavity. H. pylori exists in between the teeth and gums called “bio- film membrane” (Bio film), 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 [5,9]. 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% efficiency 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 [5].
3. 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. 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 over use [18]. The massive antibiotic pollution that appears in food, water, and children’s urine has become a serious concern worldwide. 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. This is why we recommended use non-antibiotic formula to take care on H. pylori in oral cavity.
4. There are three important technologies developing to make a strong foundation of a colonized site of the oral cavity. PCR is a high sensitivity test for oral H. pylori, but it is not convenient in clinical settings. So, first a high sensitivity and specificity test in saliva such as HPS test should be established. Then we will have a much easier time of running clinical trial on a large number of patients to obtain a greater number of data, to find the positive correlation between oral and stomach H. pylori infection [16]. Second most important technology is developing a cell culture suitable for low concentration H. pylori in the oral cavity. Because the concentration of H. pylori in stomach is five magnitudes higher than that of the oral cavity (107 CFU/mL versus102 CFU/ mL [19,20]), it would be insufficient to use conventional stomach culturing techniques for detecting oral H. pylori. After the method of a new cell culture is established, we would confirm if HPS technology can be confirmed by cell culture data [9]. As a final step, we need to develop a technology to eliminate H. pylori from the oral cavity instead of an antibiotic drug.
