Gastroenterology

Gastroenterology

Volume 136, Issue 6, May 2009, Pages 1863-1873
Gastroenterology

Helicobacter pylori in Health and Disease

https://doi.org/10.1053/j.gastro.2009.01.073Get rights and content

Helicobacter pylori is highly adapted for colonization of the human stomach and is present in about half of the human population. When present, H pylori is usually the numerically dominant gastric microorganism. H pylori typically does not cause any adverse effects, but it is associated with an increased risk of noncardia gastric adenocarcinoma, gastric lymphoma, and peptic ulcer. Disorders such as esophageal diseases and childhood-onset asthma were recently reported to occur more frequently in individuals who lack H pylori than in H pylori-positive persons. In this review, we discuss biologic factors that allow H pylori to colonize the human stomach, mechanisms by which H pylori increases the risk of peptic ulcer disease and noncardia gastric adenocarcinoma, and potential benefits that H pylori might confer to humans.

Section snippets

Helicobacter pylori as a Member of the Normal Human Microbiota

From birth to death, humans are in contact with microbes, either transiently or persistently. Virtually every mucosal and cutaneous surface in the human body is colonized by persistent residential microbes1, 2, 3, 4, 5 (Figure 1). In most niches of the human body, including the oral cavity, esophagus, colon, and skin, many bacterial species are present, and no single species predominates. The distribution of the microbes is not accidental; each niche is colonized by microbes that are either

H pylori in Human Populations

H pylori is present in human populations throughout the world. Phylogeographic studies indicate that humans have been colonized by H pylori for ≥58,000 years, since before the most recent (but prehistoric) out-of-Africa migration.15 As humans traveled around the world populating new geographic regions, they carried their ancestral H pylori with them.16 On the basis of the presence of gastric Helicobacter species (but not H pylori) in other mammals (reviewed in Solnick and Schauer17), it is

Tropism of H pylori for the Human Stomach

H pylori is highly adapted to colonize the human stomach, whereas most other bacteria cannot persistently colonize this niche. The major factors that limit bacterial colonization of the human stomach are (1) acidity, (2) peristalsis, (3) nutrient availability, (4) host innate and adaptive immunity, and (5) competing microbes. Specific features of H pylori allow it to resist each of these stresses (Table 1).H pylori resists acid by hydrolyzing urea to yield ammonia and by regulating gene

Biologic Factors That Promote the Coexistence of H pylori and Humans

Most H pylori localize within the gastric mucus layer and do not directly interact with host cells. However, some organisms adhere to gastric epithelial cells and occasionally are internalized by these cells.34 Adherence of H pylori to gastric epithelial cells stimulates numerous signaling pathways,35 and many H pylori strains secrete toxins or other effector molecules.36, 37H pylori elicits a humoral immune response,38 and tissue infiltration by mononuclear and polymorphonuclear leukocytes

Heterogeneity among H pylori

H pylori strains isolated from unrelated individuals exhibit a high level of genetic diversity (reviewed in Blaser and Berg60 and Suerbaum and Josenhans61). Nucleotide sequences of conserved genes are 92%–99% identical among different H pylori strains, but several H pylori genes are more highly diverse in sequence.62, 63, 64 In addition to variation in the sequences of individual genes among H pylori strains, there is considerable variation in gene content. One study analyzed genomic DNA from

H pylori and Gastroduodenal Disease

Although H pylori typically colonizes the human stomach for many decades without adverse consequences, the presence of H pylori is associated with an increased risk of several diseases, including peptic ulcers, noncardia gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (reviewed in Suerbaum and Michetti109 and Atherton110). What factors account for the development of these diseases in subsets of people who harbor H pylori?

The risks of peptic ulcer disease

Potential Benefits of H pylori

H pylori colonization is associated with many biologic costs to the host; conversely, a growing body of literature suggests that the absence of H pylori might also be associated with an increased risk of various diseases. An absence of H pylori could indicate that an individual was never colonized or that the organism was present earlier in life and subsequently eradicated. The idea that H pylori might actually confer benefits to humans has engendered considerable controversy among

Conclusions

The rediscovery of gastric microbiota and the first successful culture of H pylori in 1982 by Marshall and Warren opened a new chapter in human medicine.165 Early work, showing a relation between H pylori and peptic ulcer disease, changed medical practice.134 The finding that H pylori also increased the risk of gastric adenocarcinoma bolstered the view that H pylori is a human pathogen. However, it is now becoming clear that the progressive disappearance of H pylori in the 20th and 21st

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    Conflicts of interest The authors disclose the following: potential recipients of royalties for licensed products involving CagA or VacA. At present, there are no licensed commercial products involving CagA or VacA. This article does not discuss any commercial products.

    Funding Supported by the National Institutes of Health (R01 AI39657, R01 AI068009, R01GM63270), the Department of Veterans Affairs, and the Diane Belfer Program for Human Microbial Ecology.

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