Helicobacter pylori are bacteria that live in the lining of the stomach and sometimes cause stomach inflammation and ulcers. The discovery of H. pylori changed scientists’ thinking about the nature of stomach ulcers, and led to the broader study of bacteria and other pathogens (infectious agents) as possible contributors to other well-known diseases, including heart disease and some types of cancer.
In 1975, J. Robin Warren of Australia discovered the presence of helical (spiral-shaped) bacteria in the antrum, the section of the stomach that empties into the duodenum (the top part of the upper intestine) through the pyloric valve. At that time, Warren observed that the bacteria were present in 50% persons who had stomach biopsies, and that infected persons invariably showed signs of stomach inflammation. Later, he named the bacterium Helicobacter pylori after working with fellow Australian Barry J. Marshall to cultivate the species from biopsied patients.
The two scientists hypothesized that an H. pylori infection played a part in stomach disorders, including gastritis and peptic ulcers. Many of their peers in the medical community considered this hypothesis to be preposterous, since the theory that ulcers were caused by lifestyle and psychological stress was widely accepted by both the scientific community and the general public. Robin observed that no one else noticed the bacterium in affected patients before, and that for some time after its discovery, his research team was virtually alone in investigating H. pylori.
Perhaps the greatest barrier to acceptance of such a simple explanation as a bacterial infection was the simplicity of the potential cure, a course of antibiotics and acid secretion inhibitors for a serious chronic and often disabling condition. The idea of stress and lifestyle as the cause of stomach ulcers was so pervasive and impervious to new evidence that Marshall undertook drastic action, putting himself at risk to demonstrate the role of H. pylori in disease. He allowed colleagues to obtain a sample of his stomach tissue in a biopsy to show that he was free of infection, then infected himself with the bacterium and subsequently, contracted gastritis. This act of personal commitment and courage had a decisive impact on the medical profession, which began to accept his work, although the H. pylori hypothesis as a major cause of peptic ulcers did not gain worldwide acceptance until 1991.
WORDS TO KNOW
ATROPHY: Decreasing in size or wasting away of a body part or tissue.
CHRONIC INFECTION: Chronic infections persist for prolonged periods of time—months an even years—in the host. This lengthy persistence is due to a number of factors including masking of the bacteria from the immune system, invasion of host cells, and the establishment of an infection that is resistance to antibacterial agents.
COLONIZATION: Colonization is the process of occupation and increase in number of microorganisms at a specific site.
PATHOGEN: A disease causing agent, such as a bacteria, virus, fungus, etc.
Subsequent studies have shown that about half of all humans have chronic H. pylori infection, and clinical experience confirms that this infection and the consequent destruction of the stomach lining and predisposition for stomach cancer can be halted by antibiotic treatment. Thus, Warren and Marshall brought about a paradigm shift, or a fundamental change in thinking regarding the relative importance of infectious agents as opposed to psychosocial factors in the cause and origin of gastric disease. This paradigm shift in turn led to a marked improvement in the health and quality of life for the large population stomach ulcer sufferers around the world, and led to research about the possible role of infectious agents in other diseases. For example, scientists are currently studying the potential role of infectious agents in inflammation of the walls of blood vessels that could relate to heart disease and strokes.
Thus, chronic gastritis is a disorder influenced by bacterial and the genetic predispositions of the human host. A 2007 study in which gastric biopsies were evaluated showed that the presence of H. pylori is strongly associated with both acute and chronic inflammation. The presence of neutrophils (the most common white blood cell involved in immune system function and which attacks infected tissue with inflammatory biochemicals, called cytokines) on biopsy is predictive of the presence of H. pylori as well as the extent of inflamed tissue. Long-term inflammation leads to atrophy (wasting, or decreasing size) of the stomach lining. This persistent inflammation appears to be due either to a weakness in the immune system in which the predisposed individual is unable to eliminate the bacterium, or a physiological weakness in the structure of the stomach lining that fosters the growth of H. pylori colonies (populations).
As a persistent colonizer of the human stomach, Helicobacter pylori is now known to be involved in the development of gastric cancer as well as extra-intestinal diseases. Public awareness of its contribution in the development of gastric cancer is less than 15 years old. Current anti-biotic therapies against H. pylori have been limited by antibiotic resistance and recurrence of infection, probably due to the predisposing factors in susceptible individuals discussed above. Consequently, promising vaccine development programs have been mounted as an effective preventive measure. So far, however, developmental vaccines have failed the transition from animal models to human trials. H. pylori is implicated not only in gastric cancer, but also childhood lymphomas. The latter type of cancer probably could arise from the proliferation of lymphocytes in the stomach lining in the inflammatory response to chronic infection mentioned earlier. Such proliferation could raise the probability of a lymphocyte replication error that results in cancer.
Paradoxically, scientists have found an inverse association between Helicobacter pylori infection and esophageal cancer. This inverse relationship has been attributed to reduced stomach acidity that can damage the esophagus because of the atrophy of the gastric lining.
Epidemiologists might wonder about genetic or environmental factors that differentiate the 50% of the population chronically infected with the bacterium from the 50% that show no infection. Chronic infection with Helicobacter pylori illustrates the damage that can occur when the genetic variability of individuals results favorable conditions for a pathogen (disease-causing organism) that is harmless to a large proportion of the human population. The inability of the immune system and even antibiotic treatment to conclusively end the infection in these individuals can result in severe tissue damage and possibly, cancer. Perhaps the larger lesson to be taken from H. pylori infection is that humans and microbes are in a constant struggle to adapt to one another, and some of the resulting infections resemble a chronic and desultory war that eventually wears down the host. The work of Marshall and Warren is all the more important for having provided the basis for relieving a significant amount of the misery caused by this stubborn microbial foe. Marshall and Warren were awarded the Nobel Prize for the discovery of the role of Helicobacter pylori infection in the development of stomach ulcers in 2005.
Helicobacter Foundation. “H. pylori.” <http://www.helico.com/h_general.html> (accessed May 30, 2007).
Nobelprize.org. “The Nobel Prize in Physiology or Medicine 2005.” Press Release, October 3, 2005. <http://nobelprize.org/nobel_prizes/medicine/laureat> (accessed June 7, 2007).
Kenneth T. LaPensee