Title: Helicobacter pylori

 

Key words: helicobacter pylori, gastric ulceration, chronic gastritis, achlorhydria, MALT lymphoma, gastric atrophy, duodenal ulcer, neoplasia, malabsorption, food allergies, nutritional deficiency, bowel cancer, diet, red meat, animal, saturated fat, alcohol, fibre, fruit, vegetables, folate, brassica, calcium, selenium, antioxidants, refined foods, hyperinsinaemic state, colorectal cancer, sulphate-reducing bacteria, anaerobic commensals, hydrogen sulphide, desulphovibrios, ulcerative colitis, butyrate, 5-amino-salicylic acid,

 

Date: Sept 2006

 

Category: The Gut

 

Nutrimed Module:

 

Type: Article

 

Author: Morgan, G

 

Helicobacter pylori

 

Helicobacter pylori is a flagellate microorganism inhabiting the gut in up to 65% of the human population. Adhering to the epithelial layer of the stomach, it is protected from the hostile acidic intraluminal environment of the stomach by the stomach’s mucous layer and by its ability to generate alkalising ammonia through urease activity. Once established in this niche it is hard to eradicate. Infestation is usually established in childhood.

 

H. Pylori has been associated with gastric ulceration, chronic gastritis, achlorhydria, MALT lymphoma and adenocarcinoma. In certain individuals ammonia produced by H.pylori is thought to bind with antral acid receptors leading to stimulation of hydrochloric acid and gastric or duodenal ulceration. Up to 80% of gastric ulcers are associated with H.pylori infection. Immune reactions to infection lead to chronic inflammatory changes in the body of the stomach and the development of chronic gastritis, gastric atrophy and possible neoplasia. 95% of MALT lymphomas are H.pylori positive. Strain virulence may determine pathological expression - the cagA gene is present in 100% of cases of duodenal ulcer but its incidence is not increased in cases of gastric atrophy. Associated hypo- and achlorhydria are associated with maldigestion, malabsorption, food allergies and nutritional deficiencies.

 

Antibody and breath testing now makes it possible to confirm H. pylori infection. Modern triple therapy is both effective and cost-effective, obviating the necessity for surgery and prolonged medical treatment for peptic ulceration. Eradication programmes have not yet demonstrated a prospective reduced incidence of neoplastic change.

 

References

1. Cave DR (1997) Epidemiology and transmission of Helicobacter pylori infection. Gastroenterology 113:S9-S19

2. McLean VA (1997) Proceedings of the American Digestive Health Foundation International Update Conference on Helicobacter pylori. Gastroenterology 113: S1-169

3. The EuroGast Study Group (1993) An international association  between Helicobacter pylori infection and gastric cancer. Lancet 341: 1359-1362

4. IARC (1994) International Agency for Research of Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans. Infection with Helicobacter pylori. Lyon : IARC. 61:177-240 

5. Parsonnet J, et al. (1994) Helicobacter pylori infection and gastric lymphoma. N Eng J Med 330: 1267-1271

6. Ernst PB, Crowe SE, Reyes VE (1991) How does Helicobacter pylori cause mucosal damage? The inflammatory response. Gastroenterology 113: S35-S42

7. Crabtree JE, et al. (1991) Mucosal IgA recognition of Helicobacter   pylori 120 kDa protein, peptic ulceration and gastric pathology.  Lancet 341: 1359-1362

8. Emad M, et al. (1997) Helicobacter pylori and chronic acid hyposecretion. Gastroenterology 113: 15-24 

 

2. Bowel cancer

Colorectal cancer is the world’s fourth most prevalent cancer and it has been estimated that around 65% of cases are attributable to environmental factors. Diet, based on epidemiological, case-controlled and intervention studies, is thought to be one of the prime environmental factors. Red meat, animal and saturated fat, and alcohol consumption appear to be positively correlated with colorectal cancer. Higher fibre, fruit and vegetable, folate and brassica intake appear to reduce the risk. 

 

In general, intervention studies have proved disappointing and have not supported associations abstracted from epidemiologic and case-controlled studies. Thus calcium, selenium, and antioxidants are inversely associated with rates of colorectal cancer yet supplement trials have invariably proved equivocal. This may be due to the arbitrary nature of the trial’s selected endpoint, the slow pathogenetic time course, or the synergistic and interactive nature of genetic, carcinogenic and protective factors.

 

One attractive theory of causation links the typical Western lifestyle of underactivity, obesity, high consumption of refined carbohydrates, saturated fats and alcohol and low consumption of fibre, fruit and vegetables, with a hyperinsulinaemic state. IGF-1 receptors, present on colonocytes, are mitogenic and respond to insulin stimulation. Indeed, a significantly increased rate of colorectal cancer has been reported in diabetics. These facts argue for the adoption of a healthy diet and lifestyle from an early age in order to reduce the incidence of colorectal cancer.

 

References

1. Lichtenstein P, et al. (2000) Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark, and Finland. N Eng J Med 343: 78-85

2. World Cancer Research Fund in association with the American Institute for Cancer Research. (1997) Food, nutrition, and the prevention of cancer: a global perspective. Washington, DC: AICR

3. Norat T, Lukanova A, Ferrari P, Riboli E (2002) Meat consumption and colorectal cancer risk: a dose-response meta-analysis of  epidemiological studies. Int J Cancer 98: 241-56

4. Bingham SA, et al. (2003) Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into  Cancer and Nutrition (EPIC): an observational study. Lancet 361: 1496-501

5. Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms and  implications. J Nutr Biochem 10: 66-88

6. Giovanucci E (1995) Insulin and colon cancer. Cancer Causes Control  6: 164-79

7. Weiderpas E, et al. (1997) Diabetes mellitus and risk of large bowel. J Natl Cancer Inst 89: 660-1

8. Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer:   another complication of diabetes mellitus? Am J Epidemiol  147: 816-25 

 

3. Sulphate-reducing bacteria 

Sulphate-reducing bacteria (SRB) are frequent anaerobic commensals in the large bowel. In ulcerative colitis their presence is almost universal and associated with a 3-4 fold increase in the production of hydrogen sulphide. Although other hydrogen sulphide bacteria occur in the large bowel, the morbidity of ulcerative colitis has been correlated with both SRB counts and hydrogen sulphide production.

 

The most active SRBs appear to belong to the genus desulphovibrios. They are characterised by their ability to channel hydrogen production through a sulphur metabolic pathway, generating hydrogen sulphide, rather than with other anaerobes which utilise carbon-based pathways to lead to the production of methane and acetate. Other pathological pathways undoubtedly exist: 83% of cases of ulcerative colitis show invasion of the colonic mucosa by pathogenic organisms, some of them SRBs.  Butyrate is the main energy source for colonocytes. Butyrate oxidation suppression by hydrogen sulphide leads to the crypt hyperproliferation, inflammatory and degenerative changes that are seen in ulcerative colitis.

 

Reduction in sulphide levels has been found to occur with restriction of high sulphur containing foods, such as eggs, in the diet and with the use of 5-amino-salicylic acid compounds. This may be held to explain the efficacy of these treatments though the exact contribution to the pathogenesis of ulcerative colitis by SRBs is still not clear.

 

References

1. Levine J, Ellis CJ, Furne JK, Springfield J, Levitt M (1998) Fecal   hydrogen sulfide production in ulcerative colitis. Am J Gastroenterol 93: 83-87

2. Roediger WE, Moore J, Babidge W (1997) Colonic sulfide in  pathogenesis and treatment of ulcerative colitis. Digest Dis Sci  42: 1571-1579 

3. Christl SU, Eisner HD, Dusel G, Kasper H, Scheppach W (1996)  Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of  ulcerative colitis. Digest Dis Sci 41: 2477-2481

4. Christl SU, Scheppach W, Kasper H (1995) Hydrogen metabolism in the large bowel--physiology and clinical implications. Zeitschrift fur Gastroenterologie 33: 408-413

5. Pitcher MC, Beatty ER, Cummings JH (2000) The contribution of sulphate reducing bacteria and 5-aminisalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut 46: 64-72