Apr. 24, 2007 The stomach bacterium Helicobacter pylori, which causes stomach cancer and peptic ulcers, may not be all bad. According to a new study, it may help protect kids from asthma.
The study, based on an analysis of a health survey of 7,663 adults, showed that a virulent strain of H. pylori was especially associated with being asthma-free before the age of 15. People who carry the strain were 40 percent less likely to have had asthma at an early age than those who didn't carry the strain. The study also found that the microbe was associated with protection against ragweed and other allergies due to pollens and molds particularly among younger adults.
"Ultimately, the potentially protective properties of Helicobacter are consistent with one another," explains Martin J. Blaser, M.D., the Frederick H. King Professor of Internal Medicine, Chairman of the Department of Medicine, and Professor of Microbiology at NYU School of Medicine, who has been studying H. pylori for more than 20 years.
"These properties point toward a much more complex view of the organism--not just as ulcer-pathogen or cancer-pathogen, but as an organism that has its costs and benefits to us," says Dr. Blaser. "The relative costs and benefits clearly differ among individuals."
Dr. Blaser performed the study with Yu Chen, Ph.D., MPH, assistant professor in the Department of Environmental Medicine at NYU School of Medicine, a new faculty member with expertise in epidemiology.
H. pylori lives in the mucous layer lining the stomach where it persists for decades. It is acquired usually before the age of 10, and is transmitted mainly in families. Dr. Blaser's previous studies have confirmed the bacterium's link to stomach cancer and elucidated genes associated with its virulence, particularly a gene called cagA.
Over recent years, Dr. Blaser began to suspect that the organism, the dominant bacteria in the stomach, may play a role in human health as well as disease. This observation, he says, is consistent with a theory called the hygiene hypothesis. It suggests that exposure to microbial infections in early childhood prevents or diminishes the development of allergies and asthma.
Dr. Blaser has proposed that H. pylori may protect against diseases of the upper gastrointestinal tract, such as gastroesophageal reflux disease (GERD), which may lead to Barrett esophagus, a premalignant condition, and adenocarcinoma of the esophagus. All of these conditions have become more common in developed countries -- esophageal cancer of this type is the fastest rising cancer in the United States -- as H. pylori has become far less common due to improved sanitation and widespread use of antibiotics, says Dr. Blaser. (At the same time, the incidence of peptic ulcers and gastric cancer has declined in developed countries.)
Today, less than 10 percent of children carry the organism in industrialized countries, while some 90 percent of children are infected usually by age 5 in developing countries. "This bacterium has been the dominant organism in our stomach for tens of thousands of years, and it can't disappear from us without consequences," says Dr. Blaser. He says that a substantial body of work now shows that H. pylori helps protect against GERD and the conditions it leads to in the esophagus.
"The hypothesis that colonization of H. pylori, especially cagA strain, is protective of asthma risk needs to be tested by prospective studies. The findings from our study and others will collectively provide evidence," says Dr. Chen.
If the relationship between H. pylori and asthma is confirmed in other studies, which is always the yardstick of scientific validity, then it raises the question about whether "we should be trying to eliminate Helicobacter from children," says Dr. Blaser. "This is probably the first time in human history that we have children who are growing up without Helicobacter guiding their immune responses," he says. "By the repeated courses of antibiotics given to children, we are changing human microecology and we don't know what we are doing."
In the new study, Drs. Blaser and Chen evaluated whether H. pylori's protective effect against GERD could play a role in asthma, another condition sometimes associated with GERD. They used data from the Third National Health Nutrition Examination Survey (NHANES III), which was conducted from 1988 to 1994, and originally involved nearly 40,000 people. The survey included questions about a medical history of asthma, allergic rhinitis, and allergy symptoms. Nearly 8,000 of the participants were tested for antibodies to H. pylori and the cagA protein in their blood. This subgroup formed the basis of the study.
Drs. Blaser and Chen found no overall association between the presence of the cagA strain of H. pylori and current asthma status in the individuals they studied, but found an inverse association with ever having had asthma. Those with the virulent strain were 20 percent less likely to have ever had asthma compared with participants without H. pylori. In addition, the association differed quite strikingly by age of onset. It was strongest among participants who had the cagA strain of H. pylori and had had asthma before the age of 15. This result was statistically significant, meaning that the results were not likely due to chance. Those with the virulent strain were 40 percent less likely to have had asthma at a young age.
In another part of the study, they analyzed the results of allergy skin testing to six allergens, including ragweed, rye grass, and Russian thistle, among a subgroup of 2,386 adults who had the skin tests. They correlated the results with participants' H. pylori status and found the strongest association for these allergens among the younger people in the group who carried the bug. This suggested that H. pylori is involved in protection from sensitivity to pollens and molds, says Dr. Blaser.
"No one would have predicted that the presence or absence of bacteria in your stomach is associated with your sensitivity to pollens and molds," says Dr. Blaser. "But now we have that observation and we can begin to construct a model. One hypothesis is if you have H. pylori in your stomach, you have an inflammatory process that is on-going for decades, and this is skewing the immune response in a particular direction."
The study is published in the April 23, 2007, issue of Archives of Internal Medicine. The study was supported by a grant from the National Institute of Environmental Health Sciences, the National Cancer Institute, the National Institutes of Health, the Diane Belfer Program in Human Microbial Ecology, and the Senior Scholar Award of the Ellison Medical Foundation.
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