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DENIZENS OF THE DIGESTIVE TRACT:

Aid digestion // Protect the immune system // Guard against asthma, allergies, perhaps even obesity // Comprise an ecosystem that’s being knocked out of balance.

Gut Microbiota: Our Native Flora

By Lauren Ware // Illustrations by Micah Lidberg // SUMMER 2010
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gut flora

Micah Lidberg

In 1984, when a young Australian physician named Barry Marshall drank a test tube full of the bacterium Helicobacter pylori, he expected bad things to happen. Though many bacteria are harmless or even beneficial, Marshall and his colleague Robin Warren, who in 1979 had gotten the first glimpse of H. pylori near areas of inflammation in tissue samples from ulcer patients, had come to believe that this microbe actually caused peptic ulcers. Marshall, in what would make him one of the world’s most famous self-experimenters, set out to prove it.

Medical wisdom at the time had another explanation for ulcers—stress and excess acid—and in any case, scientists were certain that bacteria couldn’t survive in the stomach’s harshly acidic environment. Those views persisted despite findings from as far back as the 1950s that antibiotics were effective against at least some peptic ulcers—indirect evidence that bacteria were present and causing problems. And indeed, within five days of swilling the microbe, Marshall showed classic signs of gastritis: stomach pain, nausea and vomiting, all clinical precursors to peptic ulcer disease.

In the years that followed, Marshall and Warren’s hypothesis became widely accepted, and using antibiotics to treat H. pylori became standard practice. Yet while the researchers’ work led to a cure for a serious disease—and a Nobel Prize in Physiology or Medicine in 2005—it also had an unintended consequence. Because of the now routine purging of this long-term denizen of the human stomach, the percentage of people in developed countries who culture positive for H. pylori has decreased dramatically, while new diseases of the digestive tract—gastroesophageal reflux disease, or GERD; and esophageal adenocarcinoma, a deadly form of cancer—have emerged as if from nowhere.

The disappearance of H. pylori is a significant loss, asserts Martin Blaser, a microbiologist at New York University Langone Medical Center, who, like Marshall, has had to battle accepted scientific wisdom. “When I began to publish about Helicobacter 12 or 13 years ago and said that it was becoming extinct, it was almost heresy,” Blaser says. “But if an ancient organism goes extinct, it’s going to have consequences.”

Blaser’s argument could apply to many other microbes that also seem to be disappearing just as we begin to understand that the bacteria that inhabit us—our microbiota, which outnumber human cells 10 to one—are an intrinsic part of our health. Resident microbes help extract energy from food, stimulate the immune system and provide a buffer against invading pathogens, among other important tasks. Only recently have scientists managed to link imbalances in our microbial makeup to cancer, inflammatory bowel disease and obesity. And though we harbor populations of bacteria in and on many parts of our bodies, those in our digestive system have been studied in the greatest depth, partly because they are the most numerous and partly because it’s suspected that gut microbiota have the most intimate connections to overall human physiology.

But those connections are in flux, as changes in lifestyle and medical practices during the past century—particularly the widespread use of antibiotics—have put pressure on many human-dwelling bacteria. “We’ve rapidly changed the treaty that we established with our microbes over a very, very long time,” says Betsy Foxman, a molecular epidemiologist at the University of Michigan School of Public Health in Ann Arbor. That treaty: We would protect our microbes from extinction by giving them shelter and food, and they would contribute to our health. But we’re no longer protecting them.

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Probiotics: Microbes on the Menu?

People receive prescriptions for them and even buy foods filled with them, purportedly to restore the natural balance of their gut flora. But the jury is still out on how, and how well, probiotics work.

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hed-dossier

1. “What Are the Consequences of the Disappearing Human Microbiota?” by Martin J. Blaser and Stanley Falkow, Nature Reviews Microbiology, Nov. 9, 2009. The authors argue that our ancestral indigenous microbes, intricately linked to our physiology, are disappearing and that the consequences may include the rise of modern diseases such as asthma and obesity.

2. “A Catalog of Reference Genomes From the Human Microbiome,” by the Human Microbiome Jumpstart Reference Strains Consortium, Science, May 21, 2010. In this groundbreaking study by the Human Microbiome Project, the authors sequenced nearly all the genes of 178 microbial species from various parts of the body.

3. “Transfer of Carbohydrate-Active Enzymes From Marine Bacteria to Japanese Gut Microbiota,” by Jan-Hendrik Hehemann et al., Nature, Apr. 8, 2010. This study demonstrates that Japanese subjects’ gut microbiota acquired genes from a marine bacterium, allowing the microbes to digest components of their hosts’ regular diet: seaweed.

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