Q J Med 1999; 92: 361-364
© 1999 Association of Physicians
Editorial |
Helicobacter pylori in the faeces?
Department of Child Health
Department of Medicine & Therapeutics, University of Glasgow
Department of Microbiology, Royal Alexandra Hospital, Paisley
The most surprising thing about Helicobacter pylori is its site of residence—within the stomach. Failure of early reports of the presence of spiral gastric organisms1 to evoke much interest was probably due to a general reluctance to view the stomach as a habitat for micro-organisms because of the extreme acidity of its lumen. Marshall and Warren's `discovery' in 19822 changed that, and now, within 18 years of the cultivation of a microaerophilic flagellated spiral organism from the human stomach, H. pylori is not only regarded as the commonest chronic bacterial infection of mankind,3 but also the principal cause of duodenal ulcer disease4 and an important factor in the pathogenesis of gastric cancer.5
The ability of H. pylori to survive and thrive in the stomach is due to several factors. The organism is motile and can penetrate the gastric mucus to reach the epithelial surface. It also secretes urease, which hydrolyses urea to carbon dioxide and ammonia, thereby allowing it to surround itself with an alkaline micro-environment, facilitating survival in an acid milieu. This property has been exploited as a diagnostic tool in the CLO test and the urea breath test.
The presence of H. pylori at the gastric mucosal surface causes profound changes in gastric physiology which vary at different stages of colonization. Transient hypochlorhydria lasting for up to several months is well described in individual cases of acute H. pylori infection.6 There have also been reports of `spontaneous hypochlorhydria' in association with the development of gastritis,7 and of `epidemic hypochlorhydria' in association with H. pylori.8 Together with volunteer experiments6,9 these lend support to the view that a transient increase in gastric pH follows acute H. pylori infection.
Thereafter, chronic infection exerts variable effects on gastric acid secretion.10 In some, the gastritis is confined to the antral region of the stomach and stimulates increased release of gastrin from the antral G cells, which in turn stimulates the healthy uninflamed mucosa of the body region of the stomach to secrete excess amounts of acid, which may result in duodenal ulceration.11 In others the gastritis involves the body of the stomach and leads to atrophy, impairing its ability to secrete acid. Patients with an atrophic body-involving gastritis and hypochlorhydria have an increased risk of gastric cancer.12
H. pylori is very common in the developing world,3, where it is associated with childhood diarrhoeal disease, undernutrition13 and growth faltering.14 It has been proposed that the loss of the gastric acid barrier during acute H. pylori infection could permit the passage of other potentially enteropathic micro-organisms into the small intestine, leading to an enteropathy, diarrhoea and malnutrition, resulting in growth failure.14 In parts of the developing world, the infection is extremely common from an early age.15 High adult seropositivity rates are related to overcrowded and unsanitary childhood living conditions,16 and poor hygiene and domestic services are associated with an enhanced risk of infection.17 Cross-infection has been demonstrated by DNA fingerprinting methods, and the seroprevalence of H. pylori infection is significantly higher in spouses of patients with a duodenal ulcer than in controls.18 However there is no evidence of a link between H. pylori infection and the number of sexual partners, which suggests that spread between adults is not easy.19 Person-to-person transmission is thought to be by the faecal-oral or oral-oral routes, although the relative importance of each remains unclear.20
Four research groups have studied the correlation between infection with hepatitis A and H. pylori in an attempt to answer this question. Two contradictory Italian studies found evidence for and against a common mode of transmission.21,22 A community-based study from the UK concluded that the case for faecal-oral transmission of H. pylori was not proven, and that other modes of transmission should be considered.23 However, a study of hospital staff in the USA reported a significant correlation between the seroprevalence of H. pylori and hepatitis A, suggesting that faecal-oral transmission was likely.24 Further supportive evidence for faecal-oral spread comes from a study showing that employees in institutions caring for intellectually disabled patients have a higher incidence of H. pylori infection than the general population.25 Oral to oral spread has been suggested from the isolation of H. pylori from dental plaque26 and from saliva.27 Polymerase chain reaction (PCR) analysis of saliva from patients with proven H. pylori infection has demonstrated H. pylori-specific DNA but not conclusively shown it to be the same strain as that in the stomach.28 Moreover, dentists do not appear to be at increased risk of H. pylori.29
Culture of H. pylori in the stools of Gambian infants30 suggests that the physiology of the gastrointestinal tract in early life may favour faecal-oral transmission. The shorter intestinal transit rate of children, and the association of acute infection with hypochlorhydria,14 may permit the passage of H. pylori through the large bowel and excretion of viable micro-organisms in the stool. Support for the hypothesis that hypochlorhydria is an important factor in determining whether H. pylori can be cultured from faeces comes from experiments in ferrets colonized with H. mustelae, which induces histopathological changes in the stomach comparable to those seen in gastric H. pylori colonization in man.31 The rate of isolation of the micro-organism from the stool of infected animals was significantly increased when they were rendered hypochlorhydric.32
However, only two research groups have so far claimed to culture H. pylori from stool,30,33 and they did not genotype the isolate. Many new species of Helicobacter have been described over the last 5 years,34 which can be grouped into urease-positive and -negative species, and by site of isolation. The group of urease-positive Helicobacter spp. found in the bowel includes organisms such as H. pullorum and H. canis, raising the possibility that the organism isolated in The Gambia30 was a urease-positive enteric Helicobacter other than H. pylori.
Although it has proved difficult to culture the organism from stool, extensive indirect evidence suggests that the organism, or parts of it, can be found there. PCR amplification of H. pylori DNA is an extremely sensitive method of detection, but inhibitory substances in the stool hinder attempts to extract and amplify DNA.35 In one study of patients with proven gastric H. pylori infection, PCR successfully detected the 16SrRNA gene in 90% of faecal samples.36 However others have failed to achieve such high detection rates.37 A primer based on the 16SrRNA gene may lack the specificity needed to identify H. pylori, because this gene is conserved across a number of bacterial species. The combination of PCR and restriction fragment length polymorphism analysis of the amplified DNA provides for specific identification of H. pylori and for typing of strains.38 However, PCR for H. pylori may not be specific, and cross-reaction with other species of Helicobacter could therefore occur.39
There are also questions about the form and viability of the organism in the stool. In common with other spiral bacteria such as Campylobacter spp., H. pylori can exist in both `normal' and coccoid forms. Coccoid forms of H. pylori were described soon after its discovery, predominate in older cultures and cannot be subcultured in vitro. They may represent a viable but non-culturable form analogous to spores formed by other bacteria,40 and it may be in this form that H. pylori is excreted and survives in the environment.41 The rate of formation of the coccoid form in the stomach may be related to local nitric oxide production,42 but little is known about factors that trigger transformation during passage through the gut. It remains uncertain whether these forms of H. pylori are viable and revert to cultivable forms, or whether they represent a nonviable degenerative phase.40 Outside the stomach, the morphology, metabolism and growth behaviour of H. pylori changes, and this may be most evident when H. pylori passes in the faeces to an aerobic environment.37
Recent development of a stool antigen test (Premier Platinum HpSA; Meridian Diagnostics, Cincinnati, USA) supports the view that H. pylori is excreted in the faeces. The ELISA uses a polyclonal anti-H. pylori capture antibody, and the manufacturer claims a sensitivity of 90% and specificity of 100% compared with endoscopic identification of H. pylori. The kit detects H. pylori antigen, but this may just be a product of digestion of the organism residing in the stomach. Therefore, other than two reports of culture from the stool,30,33 there is little evidence that H. pylori survives in the colon. The origin of DNA amplified by PCR from the stool is not known, because it has not been typed and compared with H. pylori DNA from the stomach.
Many micro-organisms that colonize or infect the upper gastrointestinal tract may also be isolated from the stool. The colon is the habitat of a vast and diverse microflora, many of which take part in fermentative and other metabolic activities.43 Ingested micro-organisms that pass through the gut may be excreted unchanged (such as Salmonellae and Shigellae), chronically colonize a part of the gastrointestinal tract (such as Giardia), or reside in the large bowel and/or be excreted in forms other than in which they were ingested (such as Entamoebae). It should not come as a complete surprise, therefore, to find evidence of H. pylori in the colon, though it could be present in the stool largely in a non-cultivable (coccoid) form.
Detection of H. pylori antigens in the stool will drive researchers with new determination to culture the organism from faeces, and to try to characterize the form in which it exists in, or passes through the large bowel. It is possible that failure of attempts to repeat the culture of H. pylori from stool30,33 are because the organism does not usually survive passage through the gastrointestinal tract, except when intestinal transit is rapid and there is hypochlorhydria. It may be that the antigen test is merely detecting antigen material from dead and partially digested bacteria from the stomach.
The principal questions raised by the detection of H. pylori antigens in the stool are: where in the gastrointestinal tract does H. pylori reside and how is it transmitted? Are the types and forms of H. pylori found in the stomach the same as those in the stool and oral cavity, and does eradication of gastric infection also eliminate the organisms from these sites? If the answer to the second question is yes, then the stool antigen test could eclipse the urea breath test as a non-invasive screening test for H. pylori colonization, and facilitate epidemiological studies of its mode of transmission.
Acknowledgments
We thank Simon Ling for his helpful comments and the Children's Research Fund for its support.
References
1. Bizzozero G. Uber die schlauchformigen drusen des magendarmkanals und die bezienhungren ihres epithels zu dem oberrflachenepothel der schleimhaut. Arch Mikrobiol Anat 1893; 42: 82–152.
2. Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; i:1273–5.
3. Holcombe C, Omotata BA, Eldridge J, Jones DM. Helicobacter pylori, the most common chronic bacterial infection in Africa: a random serological study. Am J Gastroenterol 1992; 87:28–30.[ISI][Medline]
4. Anonymous. NIH consensus Conference. Helicobacter pylori in peptic ulcer disease. JAMA 1994; 272:65–9.[ISI][Medline]
5. Eurogast Study Group. An international association between Helicobacter pylori infection and gastric cancer. Lancet 1993; 341:1359–62.[ISI][Medline]
6. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol 1987;82:192–9.[ISI][Medline]
7. Hunt RH. Helicobacter pylori and spontaneous hypochlorhydria. In: Rathbone BJ, Heatley RV, eds. Helicobacter pylori and Gastroduodenal Disease. Oxford, Blackwell Scientific, 1992; 187–97.
8. Graham DY, Alpert LC, Lacey Smith J, Yoshimura HH. Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria. Am J Gastroenterol 1988; 83:974–80.[ISI][Medline]
9. Morris A, Ali MR, Nicholson G, Perez-Perez G, Blaser M. Long term follow-up of voluntary infection of Helicobacter pylori. Ann Intern Med 1991; 114:662–3.
10.
McColl KEL, El-Omar E, Gillen D. Interactions between H. pylori infection, gastric acid secretion and anti-secretory therapy. Br Med Bull 1998; 54:121–38.
11. El-Omar E, Penman I, Ardill JES, Chittajulla RS, Howie C, McColl KEL. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology 1997; 113:15–24.[ISI][Medline]
12. El-Omar E, Oien K, El-Nujumi A, et al. Helicobacter pylori and chronic gastric acid hyposecretion. Gastroenterology 1997; 113:15–24.
13. Sullivan PB, Thomas JE, Wight DGW, Neale G, Eatham EJ, Corrah T, Lloyd-Evans N, Greenwood BM. Helicobacter pylori infection in Gambian children with chronic diarrhoea and malnutrition. Arch Dis Child 1990; 65:189–91.[Abstract]
14. Dale A, Thomas JE, Harding M, Darboe MK, Coward WA, Harding M, Weaver LT. Acute Helicobacter pylori infection, gastric acid secretion and infant growth. J Pediatr Gastroenterol Nutr 1998; 26:393–7.[ISI][Medline]
15. Thomas JE, Dale A, Harding M, Coward WA, Cole TJ, Weaver LT. Helicobacter pylori infection in early life. Pediatr Res 1999; 45:218–23.[ISI][Medline]
16. Megraud F. Epidemiology of Helicobacter pylori infection. Gastroenterol Clin N Am 1993; 22:73–88.[ISI][Medline]
17. Mendall MA, Goggin PM, Molineaux N, et al. Childhood living conditions and Helicobacter pylori seropositivity in adult life. Lancet 1992; 339:896–7.[ISI][Medline]
18.
Parente F, Maconi G, Sangalletti O, Minguzzi M, Vago L, Rossi E, Bianchi Porro G. Prevalence of Helicobacter pylori infection in related gastroduodenal lesions in spouses on Helicobacter pylori positive patients with duodenal ulcer. Gut 1996; 39:629–33.
19.
Polish LB, Douglas JM, Jr, Davidson AJ, Perez-Perez GI, Blaser MJ. Characterization of risk factors for Helicobacter pylori infection among men attending a sexually transmitted disease clinic: lack of evidence for sexual transmission. J Clin Microbiol 1991; 29:2139–43.
20. Megraud F, Transmission of Helicobacter pylori: faecal-oral versus oral-oral. Ailment Pharmacol Therapy 1995; 9 (suppl 2):85–91.
21.
Luzza F, Imeneo M, Maletta M, Paluccio G, Giancotti A, Perticone F, Foca A, Pallone F. Seroepidemiology of Helicobacter pylori infection and hepatitis A in a rural area: evidence against a common mode of transmission. Gut 1997; 41:164–8.
22. Pretolani S, Stroffolini T, Rapicetta M, Bonvicini F, Baldini L, Megraud F, Ghironzi GC, Sampogna F, Villano U, Cecchetti F, Giulianelli G, Stefanelli ML, Armuzzi A, Miglio F, Gasbarrini G. Seroprevalence of hepatitis A virus and Helicobacter pylori infections in the general population of a developed European country (the San Marino study): evidence for similar pattern of spread. Eur J Gastroenterol Hepatol 1997; 9:1081–4.[ISI][Medline]
23. Webb PM, Knight T, Newell DG, Elder JB, Forman D. Helicobacter pylori transmission: evidence from comparison with hepatitis A virus. Eur J Gastroenterol Hepatol 1996; 8:439–41.[ISI][Medline]
24. Rudi J, Toppe H, Marx N, Zuna I, Theilmann L, Stremmel W, Raedsch R. Risk of infection with Helicobacter pylori and hepatitis A virus in different groups of hospital workers. Am J Gastroenterol 1997; 92:258–62[ISI][Medline]
25. Bohmer CJ, Klinkenberg-Knol EC, Kuipers EJ, Niezen-de Boer MC, Schreuder H, Schuckink-Kool F, Meuwissen SG. The prevalence of Helicobacter pylori infection among inhabitants and healthy employees of institutes for the intellectually disabled. Am J Gastroenterology 1997; 92:1000–4.[ISI][Medline]
26. Banatvala N, Romero LC, Owen RJ. Use of the polymerase chain reaction to detect Helicobacter pylori in the dental plaque of healthy and symptomatic individuals. Microb Ecol Health Dis 1994; 7:1–8.
27.
Krajden S, Fuksa M, Anderson J, Kempston J, Boccia A, Petrea C, Babida C, Karmali M, Penner JL. Examination of human stomach biopsies, saliva, and dental plaque for Campylobacter pylori. J Clin Microbiol 1989; 27:1397–98.
28. Li C, Ha T, Ferguson DA, Chi DS, Zhao R, Patel NR, Krishnaswamy G, Thomas E. A newly developed PCR assay of Helicobacter pylori in gastric biopsy, saliva and feces. Dig Dis Sci 1996; 41:2142–9.[ISI][Medline]
29. Luzza F, Maletta M, Imeneo M, Fabiano E, Doldo P, Biancone L, Pallone F. Evidence against an increased risk of Helicobacter pylori infection in dentists: a serological and salivary study. Eur J Gastroenterol Hepatol 1995; 7:773–6.[ISI][Medline]
30. Thomas JE, Gibson G, Darboe M, Dale A, Weaver LT. Isolation of Helicobacter pylori from human faeces. Lancet 1992; 340:1094–5.
31.
Fox JG, Paster BJ, Dewhirst FE, Taylor NS, Yan LL, Macuch PJ, Chmura LM. Helicobacter mustelae isolation from feces of ferrets: evidence to support fecal-oral transmission of a gastric Helicobacter. Infect Immun 1992; 60:606–11.
32. Fox JG, Blanco MC, Yan L, Shames B, Polidoro D, Dewhirst FE, Paster BJ. Role of gastric pH in isolation of Helicobacter mustelae from the feces of ferrets. Gastroenterology 1993; 104:86–92.[ISI][Medline]
33. Kelly SM, Pitcher MCL, Farmery SM, Gibson GR. Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom. Gastroenterology 1994; 107:1671–4.[ISI][Medline]
34. Kusters JG, Kuipers EJ. Non-pylori Helicobacter infections in humans. Eur J Gastroenterol Hepatol 1998; 10:239–41.[ISI][Medline]
35.
Wilde J, Eiden J, Yolken R, Removal of inhibitory substances for detection of Group A rotaviruses by reverse transcriptase and polymerase chain reactions. J Clin Microbiol 1990; 28:1300–7.
36. Mapstone NP, Lynch DA, Lewis FA, Axon ATR, Tompkins DS, Dixon MF, Quirke P, PCR identification of H. pylori in faeces from gastritis patients. Lancet 1993; 341:447.[ISI][Medline]
37.
van Zwe AA, Thijs JC, Kooistra-Smid AM, Schirm J, Snijder JA. Uase of PCR with feces for detection of Helicobacter pylori infections in patients. J. Clin Microb 1994; 32: 1346–8.
38. Jiang C, Li C, Ha T, Ferguson DA, Chi DS, Laffan JJ, Thomas E. Identification of H. pylori in saliva by nested PCR assay derived from a newly cloned DNA probe. Dig Dis Sci 1998; 43:1211–18.[ISI][Medline]
39. El Zaatori FA, Oweis SM, Graham DY. Uses and cautions of use of PCR for detection of H. pylori. Dig Dis Sci 1997; 42:2116–19.[ISI][Medline]
40. Boucher SN, Slater ER, Chamberlain AH, Addams MR. Production and viability of coccoid forms of Campylobacter jejuni. J Appl Bacteriol 1994; 77:303–7.[Medline]
41. Hulter K, Hon SW, Enroth H, KLein PD, Opekon AR, Gilmon RH, Evans DG, Engstrand L, Graham DY, El-Zaatori FA. Helicobacter pylori in the drinking water in Peru. Gastroenterology 1996; 110:1031–5.[ISI][Medline]
42. Cole SP, Eckmann L, Guiney DG, Nitric oxide mediated crosstalk between helicobacter and gastric mucosa. Proceedings of 38th Interscience Conference on Antimicrobial Agents and Chemotherapy 1998; B15–49.
43. Cummings JH, MacFarlane GT. Role of intestinal bacteria in nutrient metabolism. Clin Nutr 1997; 16:3–11.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. J Shepherd, C. L Williams, C. P Doherty, M. Hossack, T. Preston, K. E L McColl, and L. T Weaver Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the faeces with the urea breath test Arch. Dis. Child., September 1, 2000; 83(3): 268 - 270. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||