MAY 15, 2007


Is H pylori the asthma upsurge
missing link?

Stomach bug protects against allergy. More than a hygiene theory

No man is an island, said John Donne, and the presence of infectious disease would seem to prove him right on that score. But whatever sort of landmass mankind is, it is certainly one teeming with life.

Like it or not, we have evolved as symbiotic organisms, playing host to a plethora of microorganisms, many of which we haven't even named yet. The development of public sanitation, and later of antibiotics, has saved countless lives by protecting us from virulent pathogens. But these blunt instruments have also taken their toll on more cooperative microbes, with effects that are still largely unknown.

One measurable change in recent years is the growth of allergy and asthma, a development largely confined to the most developed countries, with the best sanitation and health systems. Could this be linked to reduced exposure to microbes? This is the foundation of the "hygiene hypothesis," a theory that has gained a lot of ground in recent years.

It has just gained a little more, with the publication of research in the Archives of Internal Medicine which suggests that the stomach bacterium Helicobacter pylori is actually protective against asthma and allergy.

The study, by Drs Martin Blaser and Yu Chen of New York University, looked at the correlation between H pylori status and history of allergy in 7,663 adults tested for the bacterium as part of America's Third National Health and Nutrition Examination Survey.

While they found no significant association between H pylori colonization and current asthma, they did find a clear inverse association between H pylori colonization and a history of asthma. The inverse association was particularly strong in the case of the most virulent strain of H pylori, which is identified by the presence in blood of a protein called cagA.

It was also stronger in those whose asthma developed at an early age. Those who had H pylori (cagA+) were 40% less likely to have developed asthma by age 15 than those who tested negative for the bacterium.

A subgroup of 2,386 adults who were tested for H pylori were also subjected to allergy skin testing for six allergens, including ragweed, rye grass and Russian thistle. Again, a clear pattern emerged — those who tested positive for H pylori showed less sensitivity to allergens, especially those with the cagA protein. Again, the benefit was concentrated in the young.

"We went into this study with two assumptions," says Dr Martin Blaser, chairman of the NYU Department of Medicine, who has studied H pylori for two decades. "First, that H pylori would be protective against asthma, especially the cagA variant — that proved correct. Second, that the protective mechanism was linked to H pylori's known protective effect against gastrointestinal reflux disease. That proved false."

H pylori causes peptic ulcers and, potentially, stomach cancer. But the decline of H pylori in developed countries has seen a rise in GERD, Barrett's esophagus and esophageal cancer. Several research papers have found evidence that H pylori protects against GERD. It was natural enough to assume that airway damage from GERD would lead to asthma.

But the findings on skin sensitization seem to suggest that H pylori is working at a more basic immunological level. "There seems no way that GERD could influence skin sensitization," says Dr Blaser. "It's notable that people with H pylori have a large mass of gastric lymphoid tissue which plays an important role in the development of the immune system." Stimulation of this source of immune cells may produce immunoregulatory lymphocytes that keep a lid on immune hyperreactivity.

The key point, says Dr Blaser, is that H pylori colonization is the default human state of affairs, but it's a default position we're fast drifting away from. "About 10% of the US population now has detectable H pylori colonization. I was just in Sweden and Germany, where I'm told the figure is less than 5%. The proportion in the developing world is over 50%, and just a few generations ago the levels in our own societies were 70, 80, even 90%. So H pylori is disappearing really fast, and this disappearance is almost certainly mirrored in other microorganisms we can't detect as easily."

"I wrote a paper on this a few years ago called Global Warming and the Human Stomach," he continues, "because I wanted to point out that there is a mass extinction process taking place in our micro-environment that mirrors what we're seeing in our macro-environment. We're just beginning to look at these issues seriously. We need to know what we're doing when we upset relationships that have existed for tens of thousands of years."



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