Helicobacter pylori in Health and Disease
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
References (165)
- et al.
Campylobacter pylori and Barrett's esophagus
Mayo Clin Proc
(1988) - et al.
Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid
Gastroenterology
(1990) - et al.
Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis
Gastroenterology
(1991) - et al.
Purification and characterization of the vacuolating toxin from Helicobacter pylori
J Biol Chem
(1992) - et al.
CD18 is the T-lymphocyte receptor of the Helicobacter pylori vacuolating cytotoxin
Cell Host Microbe
(2008) - et al.
Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase
Gastroenterology
(2007) - et al.
Mosaicism in vacuolating cytotoxin alleles of Helicobacter pyloriAssociation of specific vacA types with cytotoxin production and peptic ulceration
J Biol Chem
(1995) - et al.
Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo
J Biol Chem
(2002) - et al.
Grb2 is a key mediator of Helicobacter pylori CagA protein activities
Mol Cell
(2002) - et al.
A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer
Gastroenterology
(2007)
Determinants of non-toxicity in the gastric pathogen Helicobacter pylori
J Biol Chem
Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation
J Biol Chem
Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin
J Biol Chem
High resolution structural analysis of Helicobacter pylori VacA toxin oligomers by cryo-negative staining electron microscopy
J Struct Biol
Geographic distribution of vacA allelic types of Helicobacter pylori
Gastroenterology
Bacterial diversity within the human subgingival crevice
Proc Natl Acad Sci U S A
Metagenomic analysis of the human distal gut microbiome
Science
Diversity of the human intestinal microbial flora
Science
Molecular analysis of human forearm superficial skin bacterial biota
Proc Natl Acad Sci U S A
Bacterial biota in the human distal esophagus
Proc Natl Acad Sci U S A
Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis
J Clin Pathol
Role of Helicobacter pylori infection in complications from Meckel's diverticulum
Dig Dis Sci
Gastroenteritis and transmission of Helicobacter pylori infection in households
Emerg Infect Dis
Helicobacter pylori: epidemiology and routes of transmission
Epidemiol Rev
Molecular analysis of the bacterial microbiota in the human stomach
Proc Natl Acad Sci U S A
Comparative analysis of human gut microbiota by barcoded pyrosequencing
PLoS ONE
Description of ‘Candidatus Helicobacter heilmannii' based on DNA sequence analysis of 16S rRNA and urease genes
Int J Syst Evol Microbiol
Microbes on the human vaginal epithelium
Proc Natl Acad Sci U S A
An African origin for the intimate association between humans and Helicobacter pylori
Nature
Traces of human migrations in Helicobacter pylori populations
Science
Emergence of diverse Helicobacter species in the pathogenesis of gastric and enterohepatic diseases
Clin Microbiol Rev
Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly than cagA(-) strains
Gut
The cohort effect and Helicobacter pylori
J Infect Dis
Characterization of the ArsRS regulon of Helicobacter pylori, involved in acid adaptation
J Bacteriol
pH-regulated gene expression of the gastric pathogen Helicobacter pylori
Infect Immun
Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation
Science
Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging
Science
Role of the thioredoxin system and the thiol-peroxidases Tpx and Bcp in mediating resistance to oxidative and nitrosative stress in Helicobacter pylori
Microbiology
The diverse antioxidant systems of Helicobacter pylori
Mol Microbiol
Antibacterial peptide from Helicobacter pylori
Nature
Rapid genetic analysis of Helicobacter pylori gastric mucosal colonization in suckling mice
Proc Natl Acad Sci U S A
Identification and characterization of Helicobacter pylori genes essential for gastric colonization
J Exp Med
Identification of Helicobacter pylori genes that contribute to stomach colonization
Infect Immun
Recombination-based In Vivo Expression Technology identifies Helicobacter pylori genes important for host colonization
Infect Immun
The equilibria that allow bacterial persistence in human hosts
Nature
Intracellular and interstitial expression of Helicobacter pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma
J Infect Dis
Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection
Proc Natl Acad Sci U S A
Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion
Science
Campylobacter pylori antibodies in humans
Ann Intern Med
Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons
N Engl J Med
Cited by (0)
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.