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Introductory Chapter: Helicobacter pylori - An Overview of an Old Human Microorganism

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Bruna Maria Roesler

Submitted: October 24th, 2018 Published: September 18th, 2019

DOI: 10.5772/intechopen.88806

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1. Introduction

The human stomach is an unfriendly place for most infective bacteria probably due to the very low pH found in this place. However, the first isolation of a spiral-shaped, Gram-negative and microaerophilic bacterium in 1982 by Warren and Marshall [1] significantly changed the concepts of gastric microbiology.

Initially, this bacterium was named Campylobacter pyloridis, but analysis of nucleic acid sequence and ultrastructural studies besides the helical shape allowed differentiation of this genus to Helicobacter. Finally, the species was named pylori because it can be found most often in the antral mucosa, near the pylorus [2].

Helicobacter pylori (H. pylori) organisms are 2.5–5.0 μm long and 0.5–1.0 μm wide, with two to six unipolar-sheathed flagella, which are essential for bacterial motility [3]. It has been described that bacteria can exist in three different morphologic forms: the viable and culturable spiral form, the viable but nonculturable (VBNC) coccoid form which are less virulent, and the nonviable degenerative H. pylori form [4].

Colonization with H. pylori is commonly acquired during childhood and induces chronic gastritis in all infected individuals unless specific treatment is given [5, 6]. While over 80% of infected subjects remain asymptomatic [7], H. pylori chronic infection has been associated with the development of various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma [8]. In fact, H. pylori infection is a significant risk factor for the development of gastric cancer, and bacterium is classified as a group I carcinogen by the World Health Organization [9].

Although H. pylori is primarily responsible for the upper gastrointestinal diseases, only 10% of people colonized with this bacterium portray disease symptoms. It suggests that host and bacterial factors also contributed to differences in H. pylori pathogenicity [10, 11]. For instance, the risk of developing gastric cancer is also related to genetic characteristics of the host and environmental factors, which, associated with specific bacterial strain characteristics, influence the severity of the chronic inflammatory response [12, 13].

H. pylori is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than 50% of the world population [14, 15]. It has been demonstrated that H. pylori has a long period of coevolution with humans, going back at least since human migration out of Africa about 60,000 years ago [16, 17]. There are very well-characterized mechanisms of adaptation which was developed by ancestral H. pylori over the time. Through selection and coevolution, this bacterium established measures which actively and passively avoid the human immune response [18].

H. pylori infection results in recruitment of neutrophils, lymphocytes, and macrophages into the gastric mucosa through the induction of several cytokines such as TNF-α, IL-6, and IL-8 [19, 20]. It is believed that the immune response during infection plays an important role in the pathogenesis. H. pylori successfully establishes a chronic infection by achieving a delicate balance between inducing immune response and surviving in the inflammatory milieu by using an array of important virulence factors [15].

H. pylori presents important virulence factors which are essential both for bacterium colonization and maintenance in the human stomach (such as urease and flagella) and for the interaction with the gastric epithelial cells, the bacterial adhesins (blood group antigen-binding adhesion (BabA), sialic acid-binding adhesion (SabA), AlpA and AlpB, HopZ, and OipA). Besides, virulence factors involved in gastric inflammation are important for the development of chronic infection and clinical symptoms of gastrointestinal diseases (the principal are cytotoxin-associated gene-pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), and duodenal ulcer promoting gene (dupA)).


2. Epidemiology of H. pylori infection

The H. pylori infection has emerged as one of the most common chronic bacterial infections worldwide and affects more than half of the world’s population, with clinical signs of infection only manifesting in <20% of these individuals [21].

H. pylori is thought to be indigenous to the human population and is well adapted to existing in the human stomach for the lifetime of its host [22] unless eradication using appropriate chemotherapeutic agents is successful. Lifelong colonization seems to be due to the ability of some strains of H. pylori to both adapt to the host’s immunological responses and to also withstand the constantly changing gastric environment [23].

The rate of H. pylori infection differs among groups as well as within the population. Strains from different geographical areas exhibit phylogeographic features [24, 25, 26]. The genomic patters of H. pylori have been shown to be extremely diverse, and gastric mucosa may be colonized by strains with small differences in the genomic patterns suggesting subtype variation [27].

The prevalence of H. pylori infection varies widely by geographic area, age, race, and socioeconomic status. While the infection is on a fast decline in the most of the Western countries, mainly due to the success of therapeutic regimens and improved personal and community hygiene that prevents reinfection, in developing countries, the prevalence rates can reach 90% and is higher among individuals belonging to low socioeconomic status group [28, 29]. It occurs especially due to failure of treatment and emergence of drug resistance [25, 30].

Most studies suggest that males and females are infected at approximately the same rates [31, 32, 33]. In spite of it, a meta-analysis population-based study reported a male predominance of H. pylori-related diseases in adults but not in children [34].

The infection probably occurs in the childhood, and children are often infected by a strain with a genetic fingerprint identical to that of their parents [35]. Besides, local prevalence of H. pylori within a country also should be considered, and there are estimates that infection is more common in rural developing areas than in urban developed ones [36].

Moreover, differences by ethnic and racial groups are evident [31, 32, 37]. In addition, the main risk factors of H. pylori infection, especially if present during childhood, have been associated with socioeconomic status. Malaty and Graham [38] demonstrated that there is probably an inverse correlation between prevalence and socioeconomic status. It has also been reported that overcrowding, such as living in a crowded environment, sibship size, number of persons or children in the home, number of persons per room, crowding index, and living in an institutionalized population, is a situation consistently related to H. pylori positivity [39, 40, 41, 42].

Finally, it is important to consider that the pathogenetic role of H. pylori in gastroduodenal pathologies has been elucidated and confirmed in the past 30 years [43] redirecting the scientific and medical understanding of great part of gastrointestinal diseases. The development of effective therapies against H. pylori infection has progressed, and its successful eradication leads to healing of chronic active gastritis and reverses inflammation of the mucosa. In spite of it, the challenge nowadays is gastric cancer and the understanding of gastric carcinogenesis, almost always associated with H. pylori long-term infection [44].


3. Transmission pathways

Although the natural niche for H. pylori is the human stomach, some questions about other possible reservoirs for bacterium have been appearing in the last years. Nevertheless, most part of the questions about the transmission of H. pylori remains unclear, and, because of it, the possible modes of transmission are still unknown. Consequently, the routes of transmission of H. pylori are supposed to occur via an array of different pathways.

Some important studies have reported and highlighted the importance of H. pylori biofilms, the presence of coccoid forms within the biofilm, and resistance, providing insight into the prevalence of coccoid forms in the gastric mucosa. These reports are very important because these can bring a better understanding about the mechanisms behind recalcitrant coccoid states and how they can phenotypically shift into more virulent spiral forms [21, 45, 46, 47].

The infection is typically acquired in early childhood and once established commonly persists throughout life unless treated. Person-to-person transmission within the family appears to be the predominant mode of transmission, particularly from mothers to children and among siblings, indicating that intimate contact is important [29, 48, 49, 50]. The route of transmission is uncertain, but the gastro-oral, oral-oral, and fecal-oral routes are likely possibilities.

The community and environment may play additional roles for H. pylori transmission in some settings. Molecular analyses show that the microorganism is also present in various aquatic environments suggesting that human-fecal-contaminated water sources could be a plausible reservoir of the pathogen. The persistence of the environment virulent H. pylori strain in a clustered state, such as the biofilm, suggests a long-term survival of the bacterial community outside the host, enabling bacterial transmission with important clinical repercussions [21, 46]. In addition, zoonotic transmission by houseflies [51, 52, 53] and some domestic animals such as dogs, cats, and sheep [54, 55, 56], as well as iatrogenic transmission [57, 58], have been proposed. Besides, there can be factors both from host and bacterium which may modify the acquisition and persistence of H. pylori infection.

Another possibility of H. pylori transmission which has been extensively reported is the water. The contamination of drinking water by human feces has been suggested as one of the possible routes of H. pylori transmission, and it has been demonstrated that the microorganism is present in the so-called viable but nonculturable state in this unsuitable environment, meaning that their role in fecal-oral transmission via contaminated water sources cannot be disregarded [47, 59]. The first evidences of water transmission route were obtained in studies developed in some Latin American countries—Peru, Colombia, Chile, and Venezuela—and since then H. pylori has been detected in several water sources, including lakes, rivers, tap water, well water, irrigation water, and sea water, and also in water distribution systems. Consequently, it can be hypothesized that drinking water could be the pathway for returning to humans [14]. Consequently, it can be suggested that water can serve as an intermediate source in the fecal-oral transmission of H. pylori, acting as a reservoir in which this pathogen can survive for long periods.


4. H. pylori eradication therapies

The principal cases in which H. pylori have to be eradicated have been discussed in several guidelines worldwide, also considering that this microorganism is sensitive to only a few medications, and their widespread use in other kind of infections has led to a reduction in their effectiveness against the bacterium.

The infection is typically treated with combinations of two to three antibiotics along with a proton pump inhibitor (PPI), taken concomitantly or sequentially for periods ranging from 3 to 14 days. In spite of it, there is no treatment regimen which guarantees cure of H. pylori infection in 100% of patients. Individuals should be asked about any previous antibiotic uses, information that has to be taken into consideration when choosing an H. pylori treatment regimen.

Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days remains a recommended treatment option in regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no previous history of macrolide exposure for any reason. Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10–14 days is a recommended first-line treatment option. Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and nitroimidazole for 10–14 days is a recommended first-line treatment option. Levofloxacin triple therapy consisting of a PPI, levofloxacin, and amoxicillin for 10–14 days is a suggested first-line treatment option. Finally, fluoroquinolone sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI, fluoroquinolone, and nitroimidazole for 5–7 days is a suggested first-line treatment option [60, 61, 62].

This book comprehends important chapters that will certainly clarify the understanding of this microorganism infection, which affects half of the world population, despite promoting clinical symptoms and disease in only a small part of the infected individuals.


  1. 1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311-1315
  2. 2. Goodwin CS et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. International Journal of Systematic Bacteriology. 1989;39:397-405
  3. 3. Geis G, Leying H, Suerbaum S, et al. Ultrastructure and chemical analysis of Campylobacter pylori flagella. Journal of Clinical Microbiology. 1989;27:436-441
  4. 4. Andersen LP, Rasmussen L. Helicobacter pylori-coccoid forms and biofilm formation. FEMS Immunology and Medical Microbiology. 2009;56:112-115
  5. 5. Buck GE, Gourley WK, Lee WK, et al. Relation of Campylobacter pyloridis to gastritis and peptic ulcer. The Journal of Infectious Diseases. 1986;153:664-669
  6. 6. Testerman TL, Morris J. Beyond the stomach: An updated view of Helicobacter pylori pathogenesis, diagnosis and treatment. World Journal of Gastroenterology. 2014;20:12781-12808
  7. 7. Blaser MJ. Who are we? Indigenous microbes and the ecology oh human diseases. EMBO Reports. 2006;7:956-960
  8. 8. Kusters JG, van Vliet AHM, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews. 2006;19:449-490
  9. 9. IARC Working Group on the evaluation of carcinogenic risks to humans. Schistosomes, liver flukes and Helicobacter pylori. Lyon, 7-14 June 1994. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 1994;61:1-241
  10. 10. Mégraud F. Impact of Helicobacter pylori virulence on the outcome of gastroduodenal diseases: Lessons from the microbiologist. Digestive Diseases. 2001;19:99-103
  11. 11. Ahmed N, Sechi LA. Helicobacter pylori and gastroduodenal pathology: New threats of the old friend. Annals of Clinical Microbiology and Antimicrobials. 2005;4:1-10
  12. 12. Peek RM, Blaser MJ, Mays DJ, et al. Helicobacter pylori strain specific genotypes and modulation of the gastric epithelial cell cycle. Cancer Research. 1999;59:6124-6131
  13. 13. de Vries AC, Haringsma J, Kuipers EJ. The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection. Helicobacter. 2007;12:1-15
  14. 14. García A, Salas-Jara MJ, Herrera C, et al. Biofilm and Helicobacter pylori: From environment to human host. World Journal of Gastroenterology. 2014;20:5632-5638
  15. 15. Lina TT, Alzabrani S, Gonzalez J, et al. Immune evasion strategies used by Helicobacter pylori. World Journal of Gastroenterology. 2014;20:12753-12766
  16. 16. Falush D, Wirth T, Linz B, et al. Traces of human migration in Helicobacter pylori populations. Science. 2003;299:1582-1585
  17. 17. Moodley Y, Linz B, Yamaoka Y, et al. The peopling of the Pacific from a bacterial perspective. Science. 2003;323:527-530
  18. 18. Kalali B, Mejias-Luque R, Javaheri A, et al. H. pylori virulence factors: Influence on imune system and pathology. Mediators of Inflammation. 2014:1-9
  19. 19. Bodger K, Bromelow K, Wyatt JJ, et al. Interleukin 10 in Helicobacter pylori associated gastritis: Immunohistochemical localization and in vitro effects on cytokine secretion. Journal of Clinical Pathology. 2001;54:285-292
  20. 20. Lee KE, Khoi PN, Xia Y, et al. Helicobacter pylori and interleukin-8 in gastric cancer. World Journal of Gastroenterology. 2013;19:8192-8202
  21. 21. Percival SI, Suleman L. Biofilms and Helicobacter pylori: Dissemination and persistence within the environment and host. World Journal of Gastrointestinal Pathophysiology. 2014;5:122-132
  22. 22. Blaser MJ. Ecology of Helicobacter pylori in the human stomach. The Journal of Clinical Investigation. 1997;100:759-762
  23. 23. Salaun L, Linz B, Suerbaum S, et al. The diversity within an expanded and redefined repertoire of phase-variable genes in Helicobacter pylori. Microbiology. 2004;150:817-830
  24. 24. Achtman M, Azuma T, Berg DE, et al. Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Molecular Microbiology. 1999;32:459-470
  25. 25. Blaser MJ. An endangered species in the stomach. Scientific American. 2005;292:38-45
  26. 26. Ahmed KS, Khan AA, Ahmed I, et al. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: A South Indian perspective. Singapore Medical Journal. 2007;48:543-549
  27. 27. Colding H, Hartzen SH, Roshanisefat H, et al. Molecular methods for typing of Helicobacter pylori and their applications. FEMS Immunology and Medical Microbiology. 1999;24:193-199
  28. 28. van Amsterdam K, van Vliet AH, Kusters JG, et al. Of microbe and marc determinants of Helicobacter pylori-related diseases. FEMS Microbiology Reviews. 2006;30:131-156
  29. 29. Khalifa MM, Sharaf RR, Aziz RK. Helicobacter pylori: A poor man’s gut pathogen? Gut Pathogens. 2010;2:2-12
  30. 30. Ahmed N. 23 years of the discovery of Helicobacter pylori: Is the debate over? Annals of Clinical Microbiology and Antimicrobials. 2005;4:17-19
  31. 31. Goh KL. Prevalence of and risk factors for Helicobacter pylori infection in a multi-racial dyspeptic Malaysian population undergoing endoscopy. Journal of Gastroenterology and Hepatology. 1997;12:S29-S53
  32. 32. Fraser AG, Scragg R, Metcalf P, et al. Prevalence of Helicobacter pylori infection in different ethnic groups in New Zealand children and adults. Australian and New Zealand Journal of Medicine. 1996;26:646-651
  33. 33. Kawasaki M, Kawasaki T, Ogaki T, et al. Seroprevalence of Helicobacter pylori infection in Nepal: Low prevalence in an isolated rural village. European Journal of Gastroenterology & Hepatology. 1998;10:47-50
  34. 34. de Martel C, Parsonnet J. Helicobacter pylori infection and gender: A meta-analysis of population-based prevalence surveys. Digestive Diseases and Sciences. 2006;51:2292-2301
  35. 35. Covacci A, Telford JL, Del Giudice G, et al. Helicobacter pylori: Virulence and genetic geography. Science. 1998;284:1328-1333
  36. 36. Vale FF, Vitor JM. Transmission pathway of Helicobacter pylori: Does food play a role in rural and urban areas? International Journal of Food Microbiology. 2010;138:1-22
  37. 37. Bardhan PK. Epidemiological features of Helicobacter pylori infection in developing countries. Clinical Infectious Diseases. 1997;25:973-978
  38. 38. Malaty HM, Graham DY. Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection. Gut. 1994;35:742-745
  39. 39. Mendall MA, Goggin PM, Molineaux N, et al. Childhood living conditions and Helicobacter pylori seropositivity in adult life. Lancet. 1992;339:896-897
  40. 40. Goodman KJ, Correa P, Tenganá Aux HJ, et al. Helicobacter pylori infection in the Colombian Andes: A population-based study of transmission pathways. American Journal of Epidemiology. 1996;144:290-299
  41. 41. Peach HG, Pearce DC, Farish SJ. Helicobacter pylori infection in an Australian regional city: Prevalence and risk factors. The Medical Journal of Australia. 1997;167:310-313
  42. 42. Kikuchi S, Kurosawa M, Sakiyama T. Helicobacter pylori risk associated with sibship size and family history of gastric diseases in Japanese adults. Japanese Journal of Cancer Research. 1999;89:1109-1112
  43. 43. Malfertheiner P, Link A, Selgrad M. Helicobacter pylori: Perspectives and time trends. Nature Reviews. Gastroenterology & Hepatology. 2014;11:628-638
  44. 44. Roesler BM, Zeitune JMR. Molecular epidemiology of Helicobacter pylori in Brazilian patients with early gastric cancer and a review to understand the prognosis of the disease. In: Roesler BM, editor. Trends in Helicobacter pylori Infection. Rijeka: IntechOpen; 2014
  45. 45. Cellini L, Grande R, Di Campli E, et al. Dynamic colonization of Helicobacter pylori in human gastric mucosa. Scandinavian Journal of Gastroenterology. 2008:178-185
  46. 46. Hu FZ, Ehrlich GD. Population-level virulence factors amongst pathogenic bacteria: Relation to infection outcome. Future Microbiology. 2008;3:31-42
  47. 47. Cellini L. Helicobacter pylori: A chameleon-like approach to life. World Journal of Gastroenterology. 2014;20:5575-5582
  48. 48. Goodman KJ, Correa P. The transmission of Helicobacter pylori. A critical review of the evidence. International Journal of Epidemiology. 1995;24:875-887
  49. 49. Koffi KS, Attia KA, Adonis-Koffy LY, et al. Is the mother a risk factor for transmission of Helicobacter pylori infection in children between the ages of 6 months and 5 years in Còte d’Ivoire? La Medicina Tropical. 2010;70:359-363
  50. 50. Weyermann M, Rothenbacher D, Brenner H. Acquisition of Helicobacter pylori infection in early childhood: Independent contributions of infected mother, father and siblings. The American Journal of Gastroenterology. 2009;104:182-189
  51. 51. Vaira D, Holton J. Vector potential of houseflies (Musca domestica) for Helicobacter pylori. Helicobacter. 1998;3:65-66
  52. 52. Grubel P, Huang L, Masubuchi N, et al. Detection of Helicobacter pylori DNA in houseflies (Musca domestica) on three continents. Lancet. 1998;352:788-789
  53. 53. Junqueira ACM, Ratan A, Acerbi E, Drautz-Moses DI, Premkrishnan BNV, Costea PI, et al. The microbes of blowflies and houseflies as bacterial transmission reservoirs. Scientific Reports. 2017;7:16324
  54. 54. Ho SA, Hoyle JA, Lewis FA, et al. Direct polymerase chain reaction test for detection of Helicobacter pylori in humans and animals. Journal of Clinical Microbiology. 1991;29:2543-2549
  55. 55. Neiger R, Simpson KW. Helicobacter infection in dogs and cats: Facts and fiction. Journal of Veterinary Internal Medicine. 2000;14:125-133
  56. 56. Momtaz H, Dabiri H, Souod N, et al. Study of Helicobacter pylori genotype status in cows, sheep, goats and human beings. BMC Gastroenterology. 2014;14:61-68
  57. 57. Tytgat GN. Endoscopic transmission of Helicobacter pylori. Alimentary Pharmacology & Therapeutics. 1995;9(suppl. 2):105-110
  58. 58. Peters C, Schablon A, Harling M, et al. The occupational risk of Helicobacter pylori infection among gastroenterologists and their assistants. BMC Infectious Diseases. 2011;11:154-164
  59. 59. Mishra S, Singh V, Rao GR, et al. Detection of Helicobacter pylori in stool specimens: Comparative evaluation of nested PCR and antigen detection. Journal of Infection in Developing Countries. 2008;2:206-210
  60. 60. Chey WD, Leontiadis G, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori infection. The American Journal of Gastroenterology. 2017;112(2):212-239
  61. 61. Roesler BM, Costa SCB, Zeitune JMR. Eradication treatment of Helicobacter pylori infection: Importance and possible relationship in preventing the development of gastric cancer. ISRN Gastroenterology. 2012:935410
  62. 62. Manfredi M, de’Angelis GL. Eradication of Helicobacter pylori: In search of a better therapy. Clinical Microbiology. 2013:1-4

Written By

Bruna Maria Roesler

Submitted: October 24th, 2018 Published: September 18th, 2019