Gregory Kelly



Everyone new that ulcers were caused by stress, spicy food or by stomach acid. Well, everyone that is except a young Australian physician named Dr. Barry J. Marshall. He believed that bacteria called Helicobacter pylori (H. pylori) could cause peptic ulcers. Of course the medical establishment viewed this discovery as they do all new discoveries and they quickly dismissed it as "absurd".

After being ignored for years, Dr. Marshall, being so convinced that he was correct, decided to (and for those viewers at home we don't recommend that you do this) use himself as a guinea pig. Drinking the bacteria, he proved that exposure to the bacteria temporarily caused the inflammation and gastric irritation that we call an ulcer or gastritis. His ideas were eventually accepted and are now part of the dominant idea of ulcer causation (amazing how this happens).

Currently, H. pylori has been implicated in gastritis, peptic ulcer disease, gastric cancer, gastric lymphoma and recently, this organism has also been investigated in order to establish an association with heart disease.

Symptoms

Pain in the stomach area is the most predominant symptom, usually characterized as burning sensation made worse by eating for gastric ulcer and relieved by eating to return in 2-3 hours for duodenal ulcer. One third of patients with duodenal ulcers wake at night with pain and the pain tends to be episodic; lasting several days to weeks and then subsiding for weeks or months. Nausea, indigestion, gas and bloating are also common symptoms of infection. Less common symptoms include repeated vomiting and weight loss.

H. pylori might be an independent risk factor for gastric carcinoma (cancer of the stomach), auto immune disease and heart disease. Most gastric adenocarcinomas are associated with H. pylori and its presence confers an approximately six-fold increase in risk. Biopsy has demonstrated that 90% of Mucosa Associated Lymphoid Tissue (MALT) lymphomas are associated with H. pylori. Odds ratio for abnormal ECG is 3.82 for men infected with H. pylori after adjustment for a range of socioeconomic and risk factors associated with coronary heart disease.

Etiology/Epidemiology

H. pylori infection is thought to be spread by fecal/oral route. Having more than one person in a bedroom of a family house during childhood, shared beds, and no hot water in the house all increase the prevalence of H. pylori infection as an adult.

In general, the following comments can be made to summarize H. pylori prevalence in Western countries:

1. H. pylori infect about 20% of persons younger than 40, and 50% of those older than 50 years.

2. It is uncommonly found in young children.

3. Low socioeconomic status predicts infection.

4. About 92% of people with duodenal ulcer and about 70% of people with gastric ulcers are positive for H. pylori.

In developing countries most adults are infected and in parts of Africa there is 100% infection.

It is important to remember that although H. pylori is now considered to be a major cause of ulcer disease, not all individuals who have the disease show evidence of infection. Everyone who is exposed to the bacterium does not get the disease, nor do all those exposed to the organism develop long-term health problems. In fact, it is interesting to note that in parts of Africa, the prevalence of H. pylori has been shown to approach 100% and yet peptic ulcer is uncommon.

A Closer Look at H. pylori

H. pylori are a gram-negative microorganism that secretes many substances, including, ammonia, mucolytic enzymes (Adhesins, Catalase, and Urease), and acid secretion inhibitory proteins. Adhesin allows the organism to adhere (or act like Velcro and stick to gastric cells (note: this is important in its preference for O blood types)). Catalase might protect the organism from the immune system.

H. pylori increase the secretion of gastrin, which stimulates intestinal tissues to grow faster, and so could result in increased cancer risk. Urease is an enzyme responsible for hydrolyzing urea to ammonia and CO2. The CO2 may be protective by buffering pH locally. The ammonia is also protective by forming an alkaline environment around the organism. This combination of ammonia, CO2, and its acid secreting inhibitory proteins allows the bacteria to set up localized pockets where it can neutralize even the acidity of blood type O stomachs.

Blood Type Connections

Secretor/Non-secretor connections

The genetics of the secretor/non-secretor system interact to alter an individuals risk for ulcers. In several studies, non-secretors of ABO substances have been found to have a significantly higher rate of duodenal and peptic ulcers.

Because of the increased prevalence of ulcers among non-secretors, it should come as no surprise that researchers have suggested that secretor status might influence bacterial colonization density or the ability of H. pylori to attach to gastroduodenal cells.

Because non-secretors are limited in their ability to secrete blood group antigens (this is complicated stuff but trust me this is true) into the mucous secretions of their digestive tract, it has been proposed that they be at a competitive disadvantage from preventing H. pylori attachment. In other words, a non-secretor's lack of antigens in mucosal fluids might indirectly contribute to colonization by H. pylori.

In a simplified sense, when specific antigens are free floating in the mucus, it probably acts to bind up some of the H. pylori before it can contact and attach to your tissues. In essence, being a secretor provides you with an ability to put some biological decoys or metabolic false targets (in the Navy we called these false targets "chaff" and they are part of the counter measures against incoming missiles or torpedoes) out into your secretions.

Non-secretor's, as a general rule, also show a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG (H. pylori immunoglobulin G (IgG) antibody) immune response to H. pylori antigens as compared with the individuals of the secretor phenotype.

This might indicate that non-secretor's are unable to mount an aggressive immune response against this organism in comparison with their secretor brethren. Evidence does suggest that both bacterial colonization and the resultant ensuing inflammatory response are influenced, at least in part, by the ability to secrete blood group antigens. This relationship is strongest among blood type O non-secretors.

Key Point: If you are a non-secretor (especially an O non-secretor), your immune response against H. pylori appears to be lower and H. pylori appear to attach with higher aggressiveness and cause more inflammation.

Blood Type O

Like lots of other bacteria in the gut, H. pylori have a favorite blood type: Type O. I have mentioned in past columns that bacterial infection must also be thought of in terms of adhesion/anti-adhesion. Basically, in order for an infectious organism to gain a foothold it must attach to something. In simple terms think of microorganisms as if they were a piece of Velcro. Velcro will not stick to just anything (it will slide off of a smooth wood surface). In fact, Velcro is quite specific; it will only stick to special plastic with tiny projections. The microbial world of adhesion/anti-adhesion is very similar to this Velcro action. And, H. pylori is much more like molecular Velcro for the O antigen, while the A and B antigen do not give it much to stick to.



Key point: in general terms, the ability of H. pylori to attach or gain a foothold is enhanced by cells that have blood group O antigens. No wonder O's get more ulcers.



Standard Medical Strategy

The therapy recommendation for eradication of H. pylori is triple regimens comprising colloidal bismuth subcitrate (2 tablets (512mg) four times dailt with meal), either amoxicillan (2 grams/day in divided doses) or tetracycline (500 mg three times daily), and metranidazole (250 mg three times daily with meals). A minimum of two weeks seems needed for elimination of the bacteria in order to better prevent relapse within a 12-month period. Lasting remission is estimated at 84%.

Accessory Strategies

Friendly probiotic bacteria should be a key (if not the key) component of your accessory strategy. Many strains of these probiotic bacteria act as natural antagonists to H. pylori. In addition, these probiotic bacteria should always be used to enhance the effectiveness of antibiotics. Remember, probiotic bacteria are also needed to prevent antibiotic-induced disruption of the friendly bacteria in your GI.

You can also use both foods and specific lectin blocking sugars to help facilitate anti-adherence as a strategy. Since the bacteria has a preference for the O antigen, fucose, is probably the most important of these anti-adhesion sugars. The primary food sources of this sugar are bladderwrack and kelp. Both of these foods make your cells much more slippery when it comes to the molecular Velcro H. pylori uses to adhere. Another option are the Deflect products.

Bismuth is a mineral with both anti-Helicobacter pylori and ulcer healing properties. The best real world example of a bismuth product is ‘Pepto-Bismol’. Bismuth is actually very effective against this organism and is relatively safe in the doses needed to eradicate H. pylori. This is the reason for the inclusion of bismuth in standard medical treatment of H. pylori. Since bismuth (like most minerals) can be toxic if consumed in large quantities, it is recommended that you consult a physician prior to starting supplementation with bismuth compounds.

An alkaloid called berberine which is found in herbs such as Golden Seal (Hydrastis canadensis) and coptis (Coptis chinensis) has been found to inhibit the growth of H. pylori.

DGL, a form of licorice with the component that can increase blood pressure removed, has a reputation for enhancing the integrity of the mucus lining of the digestive tract. This form of licorice also appears to be antagonistic to H. pylori.

References

General

Bernersen B, Johnson R, Bostad L, Straume B, Sommer AI, Berhol P. Is Helicobacter pylori the cause of dyspepsia? British Medical Journal. 1992; 304: 1276-8.

Bland J. Applying New Essentials in Nutritional Medicine-Helicobacter pylori and upper Gastrointestinal Disease. 1994. HealthCom; Seattle WA.

Desai HG, Gill HH, Shankaran K, Mehta PR, Prabhu SR. Dental plaque: a permanent reservoir of H. pylori? Scand J Gastroenter 1991; 26: 1205-1208.

Gibson GR, Cummings JH, Kelly SM, Dunn MRC. Isolation of H. pylori from patients in the UK - implications for treatment. Gastroenterology 1994; 106, 4 (2 suppl): 81.

Krajden S, Fuksa M, Anderson J, et al. Examination of Human Stomach Biopsies, saliva, and dental plaque for Campylobacter pylori. J Clin Micribiol. 1991; 27: 1397-98.

Marshal BJ. Helicobacter Pylori. Unpublished, University of Virginia health Sciences Center. 1995.

Mendall MA, Goggin PM, Mollineux N, et al. Childhood living conditions and H. pylori seropositivity in adult life. Lancet. 1992; 339: 896-7.

Mendell MA, Goggin PM, Molineux N, et al. Relation of Helicobacter pylori infection and coronary heart disease. British Heart Journal. 1994; 71:437-39.

Miragliotta G, Fumarola D, Mosca A, Francavilla A, Monno RA. Campylobacter pylori associated gastritis and procoagulant activity production. American Society for Microbiology annual meeting 1989; abstr B222.

Parsonnet J, Blaser MJ, Perez GI, Hargrett BN, Tauxe RV. Symptoms and Risk Factors of H. pylori infection in a cohort of epidemiologists. Gastroenterology. 1992; 102: 41-6.

Parsonnet J, Friedman GD, Vandersteen DP, et al. H. pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991; 325: 1127-31.

Patel P, Mendall MA, Carrington D, Strachan DP, Leatham E, Molineax N, Levy J, Blakeston C, Seymour MA, Camm AJ, Northfield TC. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. British Medical Journal. 1995; 311: 711-14.

Soll AH. Medical Treatment of Peptic Ulcer Disease. JAMA. 1996; 275: 622-29.

Secretor/Non-secretor

Odeigah PG. Influence of blood group and secretor genes on susceptibility to duodenal ulcer. East Afr Med J 1990 Jul;67(7):487-500

Suadicani P, Hein HO, Gyntelberg F. Genetic and life-style determinants of peptic ulcer. A study of 3387 men aged 54 to 74 years: The Copenhagen Male Study. Scand J Gastroenterol 1999 Jan;34(1):12-7

Dickey W, Collins JS, Watson RG, et al. Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease. Gut 1993 Mar;34(3):351-3

Sumii K, Inbe A, Uemura N, et al. Multiplicative effect of hyperpepsinogenemia I and non-secretor status on the risk of duodenal ulcer in siblings. Gastroenterol Jpn 1990 Apr;25(2):157-61

Dickey W, Collins JS, Watson RG, et al. Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease. Gut 1993 Mar;34(3):351-3

Oberhuber G, Kranz A, Dejaco C, et al. Blood groups Lewis(b) and ABH expression in gastric mucosa: lack of inter-relation with Helicobacter pylori colonisation and occurrence of gastric MALT lymphoma. Gut 1997 Jul;41(1):37-42

Su B, Hellstrom PM, Rubio C, et al. Type I Helicobacter pylori shows Lewis(b)-independent adherence to gastric cells requiring de novo protein synthesis in both host and bacteria. J Infect Dis 1998 Nov;178(5):1379-90

Alkout AM, Blackwell CC, Weir DM, et al. Isolation of a cell surface component of Helicobacter pylori that binds H type 2, Lewis(a), and Lewis(b) antigens. Gastroenterology 1997 Apr;112(4):1179-87

Klaamas K, Kurtenkov O, Ellamaa M, Wadstrom T. The Helicobacter pylori seroprevalence in blood donors related to Lewis (a,b) histo-blood group phenotype. Eur J Gastroenterol Hepatol 1997 Apr;9(4):367-70

Heneghan MA, Moran AP, Feeley KM, et al. Effect of host Lewis and ABO blood group antigen expression on Helicobacter pylori colonisation density and the consequent inflammatory response. FEMS Immunol Med Microbiol 1998 Apr;20(4):257-66

Mentis A, Blackwell CC, Weir DM, et al. ABO blood group, secretor status and detection of Helicobacter pylori among patients with gastric or duodenal ulcers. Epidemiol Infect 1991 Apr;106(2):221-9