From the Wall Street Journal

SCIENCE JOURNAL
OCTOBER 2, 2008

The Body as Bacterial Landlord

Trillions of Microbes Living in and on Us Cause Some Harm but Also Afford Protection By ROBERT LEE HOTZ

When scientists discovered that bacteria, not stress, caused most stomach ulcers, the insight overturned a century of medical dogma, transformed clinical practice and garnered a 2005 Nobel Prize for the two researchers who made the connection so many others had missed. After people adopted antibiotics to treat gastric distress, though, microbiologist Martin Blaser and his colleagues at New York University began to document an odd medical trend.

Ulcers did drop dramatically, as expected. So did the incidence of stomach cancer. As the bacteria, called Helicobacter pylori, virtually disappeared among children, however, cases of asthma tripled. So did rates of hay fever and allergies, such as eczema. Among adults, gastric reflux disease became more common, as did some forms of esophageal cancer, researchers noted.

To Dr. Blaser’s way of thinking, antibiotics and other sanitation measures are eliminating the harm these bacteria cause at the expense of the protection they provide us.

The human body teems with so many microbes that they outnumber our own cells ten to one. Vast schools of bacteria are in us and around us, like fish nuzzling a coral reef. “They are not simply along for the ride,” says Stanford University microbiologist David Relman. “They are interacting with us.”

Yet almost all of them are still unknown to science, since most cannot be grown and studied in the laboratory. In ways mysterious to medicine, this microbial menagerie of fellow travelers in and on us is controlling our health, affecting obesity, cancer and heart disease, among others.

At this scale of biogeography, we are the world.

As many as 500 species of bacteria may inhabit our guts, like H.pylori. Maybe 500 or so other species make themselves at home in our mouth, where each tooth has its own unique bacterial colony, Dr. Relman recently determined. No one knows how many species we contain in all. This past August, researchers at Kings College London identified yet another new species of oral bacteria between the tongue and cheek.

Until recently, half of humanity harbored these H. pylori stomach bacteria, according to a 2002 study in the New England Journal of Medicine. Indeed, we appear to have evolved together. Among those born in the U.S. during the 1990s, however, only 5% or so still carry these microbes, largely due to the indiscriminate use of antibiotics.

After analyzing health records of 7,412 people collected by the National Center for Health Statistics, Dr. Blaser and NYU epidemiologist Yu Chen reported this summer in the Journal of Infectious Diseases that children between three and 13 years old who tested positive for H. pylori bacteria were 59% less likely to have asthma. They also were 40% to 60% less likely to have hay fever or rashes.

No one knows yet whether Dr. Blaser is right about H. pylori’s protective properties.

“We don’t know why the incidence of allergic disorders has increased so much,” says National Institutes of Health genomicist Julia A. Segre. “That’s why we are looking for a bacterial connection. We want to know how they are contributing to our health.”

The connection to allergies is just one of the pressing public health puzzles posed by our complex relationship with the trillions of microbes that call us home. “Recent studies have shown that changes in bacteria can be correlated with some pretty serious diseases,” says Jane Peterson, head of the National Human Genome Research Institute’s comparative sequencing program.

Childhood diabetes also is on the rise in developed countries, for instance. Last week, University of Chicago immunologist Alexander Chervonsky and his collaborators at Yale University reported that doses of the right stomach bacteria can stop the development of Type 1 diabetes in lab mice.

“By changing who is living in our guts, we can prevent Type 1 diabetes,” Dr. Chervonsky says.

Other bacteria are just as crucial to our well-being, feeding us the calories from food we can’t digest on our own, bolstering our immune systems, tending our skin and dosing us with vitamins, such as B-6 and B-12, which we are unable to synthesize unaided.

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In May, researchers led by Dr. Julia A. Segre at the National Human Genome Research Institute took inventory of the microbes living in and around your skin in “A diversity profile of the human skin microbiota,” published by Genome Research.

Last year, the National Institutes of Health launched a 5-year, $125 million Human Microbiome Project to analyze hundreds of microbial species that make your body their home. Scientists outlined the project’s research strategy in Nature.

Making the project possible is a new gene-mapping technique called metagenomics. The National Academy of Sciences explored its potential in The New Science of Metagenomics and its broader applications in Understanding Our Microbial Planet.

New York University microbiologist Martin Blaser studied the link between stomach bacteria and childhood asthma in “Helicobacter pylori Colonization Is Inversely Associated with Childhood Asthma,” published by the Journal of Infectious Diseases.

Common stomach bacteria also can stop the development of Type 1 diabetes in lab mice, researchers reported this week. The researchers believe their findings could one day be used to develop bacteria-based treatments for patients.

For the first time, researchers are attempting to identify and analyze the types of bacteria that live within us, in an effort that makes the Human Genome Project look like child’s play. Instead of sequencing the genes of one microbe at a time, researchers in a five-year, $125 million NIH effort called the

Human Microbiome Project are analyzing entire communities of mixed bacteria at once, in a technique called metagenomics.

To start, researchers at the Baylor College of Medicine in Houston, the Washington University School of Medicine in St. Louis, the Broad Institute in Cambridge, Mass., and the J. Craig Venter Institute in Rockville, Md., are sequencing the genomes of 200 microbe species isolated from 250 healthy volunteers. They are sampling bacteria from the skin, gut, vagina, mouth and nose, then attempting to identify them by cataloging variations in a single gene sequence that all bacteria share.

Working with similar metagenomics projects in Europe, Japan, China and Canada, they hope to assemble a reference collection of genomic information covering 1,000 microbial species that infest us. If all goes as planned, they may soon find themselves trying to analyze 200,000 genes, compared to only 20,000 for the human genome. “These data sets we will be generating are huge, and we don’t have the tools yet to analyze them,” says Dr. Peterson.

The diversity is more than anyone expected. Dr. Segre, who specializes in the study of the skin, found one set of microbial communities thriving in the bend of the typical elbow and an entirely different set of colonies on the average forearm. In all, she identified 113 different kinds of bacteria living in concentrations of about 10,000 per square centimeter on the surface and, just beneath the skin, in densities of one million microbes per square centimeter, she reported last May.

In a real sense, the history of all these many microbes is the history of humanity itself. “We are living beings that co-evolved with micro-organisms,” Dr. Segre says. Evidence suggests that strains of helicobacter bacteria evolved along with humankind from its beginnings in primitive organisms a billion years ago. Every mammalian species appears to have its own unique variety of these microbes.

Helicobacter pylori accompanied our ancestors on every journey. The human varietals spread from East Africa about 58,000 years ago as anatomically modern humans also first began to migrate from the region, molecular epidemiologists at the Max Planck Institute for Infection Biology in Berlin reported last year in the journal Nature. They identified 370 strains of the bacteria that seemed to reflect the migrations and settlements of their human hosts.

Most of us learn early to think of all micro-organisms as harmful germs. The thought of our intimate zoo, therefore, may make some of us reach reflexively for the antiseptic. In the U.S. alone, antibacterial products account for about $1 billion in sales annually. It is unclear, though, how long we could survive without each other.

“They live with us, and they are part of us,” says Dr. Chervonsky. “That does not mean there is no tug of war.”

Printed in The Wall Street Journal, page A17