Alfred W. Garbutt III, D.C., Inc.

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Technical Publications

In 1982 the Australian researchers, Robin Warren and Barry Marshall proved that the bacillus, Helicobacter pylori was responsible for most gastroduodenal ulcers. For this discovery they were awarded the 2005 Nobel Prize for Physiology or Medicine.
(1) The organism they isolated in the antrum / pylorus of the stomach is a gram-negative rod shaped helical bacterium. Prior to this the bacillus was unknown and it was commonly believed that stress, smoking and certain dietary habits were the cause of most ulcers.

There is usually a 6.0-6.5 pH in the oral cavity and a 10,000 time more acidic environment of 1.5-2.5 pH in the stomach. There are about 35 million parietal cell glands throughout the stomach secreting about 2-3 quarts of hydrochloric acid per day for the purpose of digesting food and minimizing pathogen infiltration to the intestinal system. Despite this highly acidic level in the stomach, H.pylori can survive when most other bacteria will not. Now the stomach itself is protected from its own hydrochloric acid and pepsin by the gastric epithelial cells secreting a thick mucus coating, which endures the low pH. If this mucus coating is breached then the acid and protein digesting pepsin will irritate the gastric lining and some level of gastritis or ulceration will develop. H.pylori survives this highly acid environment by using the urease enzyme to catalyze urea to ammonia thus creating an ammonia envelope around itself. (2) Ammonia is an acid neutralizing alkaline compound, which protects the bacterium for the acid.

Next using the mucolytic enzymes, bacterial protease and lipase, the H.pylori degrades the mucus lining which exposes the epithelia lining to acid and digestive enzyme damage then it can burrow into the epithelium. In addition to this the cytokine response to resultant inflammation can further oxidative stress damage to the mucosal layer, which can lead to ulceration. (3) Once to the epithelial lining it uses two unique proteins on its surface to adhere to the lining cells. One of these is, BabA (blood group antigen binding adhesion), which mediates the adherence of the bacteria to human blood group antigens located on gastric epithelium. (4) (5) These proteins can also inhibit the immune system response to them, thus keeping them safe from attack.

There are also several mechanisms by which H.pylori affects gastric secretion. It
can change gastric regulatory physiology by causing a rise in plasma gastrin levels and by decreasing gastric mucosal release of somatostatin, a peptide, which has the capacity to inhibit the release of insulin and somatrophin from the anterior pituitary. There may also be a gastric mucosal atrophy with parietal cell loss. It has been observed that when there is an infection with atrophy and with a low acid secretion there is a greater occurrence of gastric cancer of the intestinal-type and that duodenal ulcers are associated with an infection that has little atrophy and a high acid secretion. (6)

H. pylori have a cytotoxin-associated gene (cag A) that causes a secretion from the H. pylori cytoplasm into the host’s gastric epithelial cells. (7) There can be cagA – and + genes in H. pylori. Patients with the cagA+ gene strain of H. pylori were four times more likely to have pyloric area intestinal ulcers along with chronic gastric inflammation, polymorphic activities, degeneration of the surface epithelium and metaplasia of the intestines. (8) There is also a gene called vascuolating cytotoxin gene that is responsible for creating vacuole lesions in the tissues.
Research suggests that the adherence of H. pylori due to BabA permits an efficient delivery of vacA and cagA to the gastric cells. The strains that do this are more virulent and often associated with the cases of distal gastric adenocarcinoma. (9)

10-40 % of the people in western countries experience upper abdominal pain or discomfort over the year. (10) According to the ASHP Commission on Therapeutics, there are between 500,000 and 850,000 new cases of peptic ulcers diagnosed each year and that 10% of the American population have had peptic ulcers during their lifetime. (11) There are over one million annual hospitalizations secondary to an ulcer related event. (12) Of these peptic ulcers, approximately 80% are secondary to H.pylori infection. (13) The Centers for Disease Control and Prevention have estimated that of all duodenal ulcers that 90% were linked to H. pylori infection. Even though 50% of the world’s population is estimated to have an H.pylori infection (14) only 10-20% of the carriers have or will develop gastric diseases. These diseases can range from gastritis to ulcers to mucosa-associated lymphoma or adenocarcinoma (15). There is a 4-to-6-fold risk increase of developing stomach cancer with H. pylori infections. (16) Some key factors, which increase virulence are, secretion of large quantities of urease, amount of bacteria mobility, quality of adhesions to gastric epithelium, presence of cagA and vacA. (16).

Gastritis is an inflammation of the stomach mucosal lining and depending upon the amount of mucosal injury it is classified as erosive or nonerosive. With acute gastritis the antrum and corpus of the stomach will show polymorphonuclear cell infiltration. In chronic gastritis there is decreased mucosa functional capacity associated with some degree of tissue atrophy or metaplasia. The antrum region is usually the area of involvement and there becomes a decrease of G cells and gastrin secretion. When the corpus is involved there is a decrease of hydrochloric acid, pepsin and intrinsic factor secondary to loss of oxyntic glands. (2) The decrease of intrinsic factor will probably cause a vitamin B12 malabsorption problem along with other nutritional deficiencies caused by less efficacious digestion. Health care practitioners should bear this in mind when developing a clinical nutrition program for a patient with gastritis. Even though some patients may be asymptomatic, chronic gastritis may manifest as nausea, unexplained vomiting, upper abdominal bloating and / or acute pain.

Meta-analysis (critical survey) has shown that indigestion or dyspepsia is associated with H. pylori and that people with an infection are 60% more likely to have non-ulcer related dyspepsia than people without an H.pylori infection. (17)

Patients with gastro esophageal reflux disease (GERD) are more likely to experience symptomatic relapse of GERD sooner if they have an H.pylori infection than people that have had GERD but are not infected. (18) Even though halitosis can stem from nasal passage or respiratory tract infections, liver or kidney failure, uncontrolled diabetes and occasionally acid reflux, the dental and medical experts feel that the majority of the cases are from when certain oral bacteria break down amino acids, such as, methionine, cysteine or lysine. Research performed in Turkey in which patients with non-ulcer dyspepsia and were infected with H. pylori were treated with the conventional “triple therapy” and 97.2% of the subjects had their halitosis eradicated. (19) The “triple therapy” is usually comprised of a seven day course of a stomach acid inhibiting drug
(omeprazole or lansoprazole) called a proton pump inhibitor and two different antibiotics, usually clarithromycin and metronidazole or amoxicillin or tetracycyline. (20) Why exactly this result occurred was not totally clear but investigating the need for anti-H, pylori treatment may be indicated in chronic halitosis.

There has been a case study that compared 111 coronary heart disease (CHD) patients with 74 controls without CHD. Of the patients with CHD, 59% had evidence of H. pylori infection while the non-CHD controls had a rate of 39% infection. (21) There have been additional studies demonstrating a link with H.pylori and CHD. (22) (23) A study recently published in The journal, Digestive disease and sciences reported “direct evidence for an association between chronic H.pylori infection and insulin resistance.” (24)
Research by Santamaria, et al. has shown an association with oral H.pylori and the recurrent upper gastrointestinal bleeding and pain in children. (25) Research in Japan showed that the “triple therapy” type regime was at least 91.6% effective when the bacteria were not measurably present in the mouth and only about 52.1 % effective when oral H.pylori were detected. (26) German researchers have shown that children can become infected with H.pylori if their parents are infected. (27) The rate of infection for a child was approximately 3.9 times greater if the mother tested positive for H. pylori and 2.8 times greater for a positive father as compared to children of non-infected parents. (27) These odds ratios are important and a child of an infected parent should also be evaluated. According to a study published in the Lancet, young children (4-9 years of age) are at a greater risk of acquiring an H.pylori infection than young adults (21-23 years of age). Once infected there is a tendency to remain infected at a rate of 84%? (28) Even though these infections in children may cause gastritis with these children they may persist into adulthood where they contribute to lifelong diseases, such as, ulcers or stomach cancer.
H.pylori can be spread through oral infection. Activities, such as, sharing drinking or eating utensils, kissing and the consumption of water, meat, sea food or vegetables (Schorr M. H.pylori “ulcer bug” can be found in store-bought food. Reuters Health, May 23, 2002.) that are contaminated with the bacterium can infect a person. Of these, the person-to-person route is the most common. Therefore, safe food preparation and good personal hygiene are an essential defense mechanism to minimize acquiring H.pylori infection or further spreading of it to others.

The CDC estimates that there are over 3 million Americans and 67 million people world wide with glaucoma, which is the second leading cause of blindness. (CDC Fact Sheet for Health Care Providers. Helicobacter pylori. July 1998.) Greek physicians conducted a study that showed 88% of the glaucoma patients tested had an H.pylori infection while the control group had a 47% infection rate, which would be about the average for infection in the general population. (29) This research further showed a statistical improvement in their glaucoma when the positive subjects were treated for H.pylori.

Despite the “triple therapy” proving itself to be effective against H. pylori, 42% of the patients have experienced side effects. (30) The side effects make it difficult for some patients to comply while another concern by the medical community is the issue of drug resistant strains of H.pylori. (31) There has been research in Iran that also showed a 20% rate of resistance of Helicobacter pylori to the antibiotic tested. (32)

A non-pharmaceutical alternative for killing H. pylori is substance that has been used as an antimicrobial for thousands of years. This substance is mastic gum.
(33) (34) Mastic gum is a natural whitish resin from the Pistacia lentiscus tree, which is an evergreen shrub from the pistachio family. This tree is only found on the Greek island of Chios or Hios in the Aegean Sea. In addition to its medicinal uses it is used in the paint industry, cosmetics, paint varnish, artist color oils, the food industry for flavoring liqueurs, ice cream, chewing gum and in Greek and Arabic breads, cheeses, milk, cookies and candies.

The famous Roman physician, Galen, Aristotle and the Turkish born Greek surgeon and botanist, Dioscorides, who created the pharmacological treatise De Materia Medica, all wrote of the medicinal uses of mastic gum. British researchers in 1998 published an article about mastic gum’s 99.9% kill rate of H.pylori in an overnight incubation. (35) As little as one gram per day for two weeks has shown to relieve the symptoms of gastric ulcers. A common therapeutic dose is one gram in the morning and one before sleep for 2-4 weeks. A maintenance dose for dyspepsia is 500 mg. per day. In addition to its ability to kill H.pylori mastic gum has shown that it also has antimicrobial properties against Staphylococcus aureus, Escherichia coli, Sarcina lutea, Candida albicans, Candida parapsilosis, Torullopsis glabrata and Cryptococcus neoformans. (36) Chewing gum and toothpaste with mastic gum can be used to assist with controlling oral H. pylori in addition to the ingestion of capsules of it.

Even though a significant amount of research has been performed world wide on H.pylori, the average doctor does not pay adequate attention to this bacteria’s involvement in human dis-ease. One should consider H.pylori as a potential stressor with any oral and / or gastrointestinal complaint. Since mastic gum has no reported side effects, it should be consider as an effective antimicrobial against it.

1. Ahmed N. 23 years of discovery of Helicobacter pylori: is the debate over? Annals of Clinical Microbiology Antimicrobials. 2005 Oct 31; 4: 17.
2. Merck Manual of Diagnosis and Therapy, 17th ed. Merck research Laboratories, Whitehouse Station, NJ, 1999, pp 245-255.
3. Xia HH, Talley NJ. Apoptosis in gastric epithelium induced by Helicobacter pylori infection: implications in gastric carcinogenesis. Gastrenterol 2001; 96: 16-20.
4. Yu J, Leung WK, Go My, et al. Relation between Helicobacter pylori babA2 status with gastric epithelial cell turnover, premalignant and malignant gastric lesions. Gut.2002 Oct; 51(4): 480-4.
5. Gatti LL, Fagundes e Souza EK, Leite KR, et al. cagA vacA alleles and babA2 genotypes of Helicobacter pylori associated with gastric disease in Brazilian adult patients. Diagn Microbiol Infect Dis. 2005 April; 51(4):231-5.
6. Calam J. Helicobacter pylori and hormones. Yale J Biol Med. 1996 Jan-Feb; 69 (1):39-49.
7. Wu H, Nakano T, Daikoku E, et al. Intrabacterial proton-dependent CagA transport system in Helicobacter pylori. J Med Microbiol 2005 Dec; 54 (Pt) 12: 1117-25
8. Warburton VJ, Everette S, Mapstone NP, et al. Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis. J Clin Pathol. 1998 Jan; 51 (1): 55-61.
9. Prinz C, Schonger M, Rad R, et al. Key importance of Helicobacter pylori adherence factor blood group antigen binding during chronic gastric inflammation. Cancer Res. 2001 Mar 1; 61(5):1903-9.
10. Thijs JC, Kleibeuker JH. The management of uninvestigated dyspepsia in primary care. Minerva Gastoenterol Dietol 2005 Sep; 51 (3):213-24.
11. ASHP Commission on Therapeutics . ASHP therapeutic position statement on the identification and treatment of Helicobacter pylori-associated peptic ulcer disease in adults. Am J Health Syst Pharm 2001; 58:331-7.
12.Centers for Disease Control and Prevention, Division of Bacterial and Mycotic Diseases. Helicobacter pylori and peptic ulcer disease. www.cdcgov/ulcer).
13.Peterson WL, Ciociola AA, Sykes DL, et al. Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. Ailment Pharmacol Ther 1996;10:251-61.
14. Goodwin CS, Mendall MM, Nothfield TC. Helicobacter pylori infection. Lancet 1997;134:265-9.
15. Hocker M, Hohenberger P. Helicbacter pylori virulence factor—one part of the picture. Lancet 2003 Oct 11;362(939):1231-3.
16. Penta R, De Falco M, Iagquinto G, De Luca A. Helicobacter pylori and gastric epithelial cells: from gastritis to cancer. J Exp Clin Cancer Res 2005 Sep; 24(3): 337-45.
17. Jaakkimainen EL, Linton A, Boyle E, Tudiver F. Is helicobacter pylori associated with non-ulcer dyspepsia and will eradication improve symptoms? A met-analysis. BMJ 1999;319:1040-4.
18. Schwizer W, Thumshirm M, dent J, et al. Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomized controlled trial. Lancet 2001; 357:1738-42.
19. Serin E, Gumurdulu Y, Kayaselcuk F, et al. Halitosis in patients with Helicobacter pylori-positive non-ulcer dyspepsia: an indication for eradication therapy? Eur J Int Med 2003;14:45-8.
20. Gisbert JP; Gisbert JL, Marcos S, et al. Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin. Aliment Pharmacol Ther 2005 Nov 15;22(10): 1041-6.
21. Mendall MA, Goggin PM, Molinezus N, et al. relation of Heliobacter pylori infection and coronary artery disease.Brit Heart J 1994; 71(5):437-9.
22. Niemela S, Karttunen T, Korthonen T, et al. Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations? Heart 1996; 75(6):573-5.
23. Danesh J, Youngman L, Clark S, et al. Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. Brit Med J 1999;319(30(:1157-62.
24. Aydemir S, Bayraktarogolu T, Sert M, et al.. The effect of Helicobacter pylori on Insulin Resistance. Dig Dis Sci 2005 Nov; 50(11): 2090-3.
25. Santamaria MJ, Varea Calderon V, Munoz Almagro MC. Dental plaque in Helicobacter pylori infection. Ann Esp Pediatr 1999 Mar; 50(3):244-6.
26. Miyabayashi H, Furihata K, Shimizu T, et al. Influence of oral Helicobacter pylori on the success of eradication therapy against gastric Helicobacter pylori. Helicobacter 2000 Mar;5(1):30-7.
27. Rothenbacher K, Winkler M, Gonser T, et al. Role of infected parents in transmission of Helicobacter pylori to their children. Ped Infect Dis J 2002;21:674-9.
28. Malaty HM, El-Kasabany A, Graham DY, et al. Age at acquisition of Helicobacter pylori infection: a follow-up study from infancy to adulthood. Lancet 2002;359:931-5.
29. Kountouras J, Mylopoulos N, Chatzopouleos D, et al. Eradication of Helicobacter pylori may be beneficial in the management of chronic open-angle glaucoma. Arch Intern Med 2002;162:1237-44.
30. Reilly TB, Ayers RCS, Poxon V, Walt RP. Helicobacter pylori eradication in a clinical setting: success rates and the effect on the quality of life in peptic ulcer. Aliment Pharmacol Ther 1995;483-90.
31. Toro C, Garcia-Samaniego J, Carbo J, et al. Prevalence of primary Helicobacter pylori resistane to eigth antimicrobial agents in a hospital in Madrid. Rev Esp Quimioter 2001 Jun;14(2): 172-6.
32. Mohammadi M, Doroud D, Mahajerani N, Massarrat S. Helicobacter pylori antibiotic resistance in Iran. World J Gastroenterol 2005 Oct 14; 11(38): 6009-13.
33. Carson CF, Riley TV. Non-antibiotic therapies for infection. Commun Dis Intell. 2003;27 Suppl: S143-6.
34. Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Piatacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol 1986; 15:271-8.
35. Huwez FU, Thirlwell D, Cockayne A, et al. Mastic gum kills Helicobacter pylori. N Eng J Med 1998; 339:1946.
36. Iauk L, Ragusa S, Rapisarda A, Franco S, et al. In vitro antimicrobial activity of Pistacia lentiscus L extracts: Prelimianry report. J Chemother 1996;8:207-9.

Copyright © 2002 Alfred W. Garbutt, III, D.C., Inc.