Helicobacter pylori is a common bacterium that colonizes the human stomach and is linked to several gastric conditions, including chronic gastritis, peptic ulcers, and a heightened risk for stomach cancer. The widespread nature of H. pylori raises questions about how people become infected and why health outcomes differ so much. Understanding this involves examining human genetics, the bacterium’s own genetic diversity, and patterns of infection within families.
How H. pylori Infection Occurs
The acquisition of H. pylori is an infectious process, not a condition inherited through genes. The bacterium is transmitted from person to person through direct contact, including the oral-oral route (saliva) and the fecal-oral route from contaminated food or water. These transmission modes underscore the role of environmental factors in the spread of the bacterium.
Infection is most often acquired during childhood, and certain conditions increase the risk of exposure. Living in crowded households facilitates close person-to-person contact, raising the likelihood of transmission. Inadequate sanitation and lower socioeconomic status are also strongly associated with a higher prevalence of infection, as these circumstances can lead to greater environmental contamination.
The presence of H. pylori begins with environmental exposure rather than being predetermined by genetics. However, a person’s biological characteristics influence what happens after exposure. This distinction is important for understanding the roles that both environment and genetics play in H. pylori-related diseases.
The Role of Human Genetics in H. pylori Susceptibility
While exposure to H. pylori is necessary for infection, an individual’s genetic makeup plays a part in determining their susceptibility to colonization and the clinical outcome. Not everyone exposed to the bacterium becomes chronically infected, and the severity of the disease varies widely. This variability can be attributed to genetic polymorphisms—differences in DNA sequences among individuals that alter the function of certain genes.
The human immune response to H. pylori is an area where genetic factors are influential. Polymorphisms in genes that code for cytokines—proteins that mediate inflammation—can affect the intensity of gastric inflammation. For example, variations in the genes for interleukin-1 beta (IL-1B) and tumor necrosis factor-alpha (TNF-α) are associated with a more robust inflammatory response, increasing the risk of severe gastritis or peptic ulcers. Variants in the gene for interleukin-10 (IL-10), an anti-inflammatory cytokine, can also modify disease risk.
Beyond the immune system, genes involved in protecting the stomach lining also contribute to susceptibility. The gastric mucosa produces a mucus layer that acts as a physical barrier, and variations in genes like MUC1 can influence this barrier’s effectiveness. H. pylori must also attach to stomach lining cells to establish a persistent infection, using specific cell surface receptors to do so. The presence and structure of these receptors, such as the Lewis b blood group antigen, are determined by an individual’s genes, impacting the bacterium’s ability to colonize.
Genetic Diversity of H. pylori Strains
The clinical consequences of an H. pylori infection are not solely dependent on the host’s genetics; the characteristics of the infecting bacterial strain are also a factor. H. pylori is a highly diverse bacterial species, and different strains possess unique genes that influence their ability to cause disease. This genetic variability helps explain why some infected individuals remain asymptomatic while others develop serious conditions.
A primary example of this diversity lies in specific virulence factors—molecules produced by the bacterium that enhance its ability to cause damage. One of the most studied is the cytotoxin-associated gene A (CagA), and strains of H. pylori that carry it are considered more virulent. Once the bacterium attaches to stomach cells, it can inject the CagA protein into them, disrupting cellular processes, promoting inflammation, and increasing the risk for peptic ulcers and gastric cancer.
Another virulence factor is the vacuolating cytotoxin A (VacA), a protein that damages host cells by causing the formation of vacuoles. The gene for VacA is present in nearly all H. pylori strains, but it has different variants that produce toxins with varying levels of activity. The specific combination of CagA and VacA variants in a given strain correlates with the severity of the resulting disease.
Familial Aggregation of H. pylori: Unraveling Genes and Environment
H. pylori infection often clusters within families, which can create the impression that it is hereditary. This pattern involves an interplay between shared environmental factors and potential genetic predispositions. This clustering highlights how both exposure and susceptibility contribute to the infection’s distribution.
The primary driver of this clustering is intrafamilial transmission. Due to close and frequent contact, the bacterium can easily spread between family members, such as from a parent to a child or between siblings. This person-to-person spread is amplified by shared living conditions, which aligns with the known transmission routes of the bacterium.
At the same time, shared human genetics contribute to these familial patterns. Since family members share genetic makeup, they may also share susceptibilities that make them more prone to colonization by H. pylori. For instance, if a family shares genetic variants that lead to a less effective mucosal barrier or a particular inflammatory response, multiple members might develop similar clinical outcomes. This combination of frequent exposure and shared biological vulnerabilities explains why the infection and its consequences often run in families.