Sunday, July 17, 2011

The Trillions of Microbes That Call Us Home

by Michael Tennesen

In the intensive care nursery at Duke University Medical Center, doctors and nurses attend to premature infants in rows of incubators surrounded by ventilators and monitors. As new parents holding packages of breast milk watch their tiny babies, neo­natologist Susan LaTuga makes her rounds, checking vital signs and evaluating how the infants tolerate feeding. She consults with nurses, dietitians, and pharmacists about the course of the day’s treatment for the babies, some of whom weigh as little as one pound and were born as much as 17 weeks early.

At the end of her shift, LaTuga stops at a freezer and inspects stool samples from some of the infants that are at the center of a remarkable new study. Across the Duke campus, technicians are waiting to analyze them with a powerful gene sequencer capable of penetrating the hidden world of the billions of microorganisms growing inside each infant.

LaTuga is one of several medical researchers at Duke working with microbial ecologists to study the development of the human microbiome—the enormous population of microbes, including bacteria, fungi, and viruses, that live in the human body, predominantly in the gut. There are 20 times as many of these microbes as there are cells in the body, up to 200 trillion in an adult, and each of us hosts at least 1,000 different species. Seen through the prism of the microbiome, a person is not so much an individual human body as a superorganism made up of diverse ecosystems, each teeming with microscopic creatures that are essential to our well-being. “Our hope is that if we can understand the normal microbial communities of healthy babies, then we can manipulate unhealthy ones,” LaTuga says.

The Duke study is just one of many projects begun in the past five years that use genetic sequencing to explore how the ­diversity of the microbiome impacts our health. Two of the largest efforts are the Human Microbiome Project, funded by the National Institutes of Health, and the European Union’s Metagenomics of the Human Intestinal Tract. Although these groups have only just begun to publish their findings, it is already clear that the micro­biome is much more complex and very likely more critical to human health than anyone suspected. Understanding and controlling the 
diversity of our germs, as opposed to assaulting them with anti­biotics, could be the key to a range of future medical treatments.

In-depth analysis of the human body’s microflora has been possible only in the past few years—a by-product of the same new gene sequencing techniques that have allowed scientists to cheaply and accurately identify the DNA of the human genome. “Gene sequencing has opened a huge door to how complex these communities are,” says Patrick Seed, a Duke pediatrician specializing in infectious disease, who with biologist Rob Jackson is a lead investigator of the premature infant study.

Before sequencing was available at a reasonable price, microbes were identified by growing them in a petri dish. But “not all microbes will grow in culture,” LaTuga says. “It identifies only about 20 percent of the microbes in the gut.”

Like a lush rain forest, a healthy microbiome in the human gut is a diverse ecosystem that thrives only when all the interdependent species are healthy too. “In an ecological sense, more diverse communities are healthy on land and in the seas,” Jackson says. “No one species is dominant, and the ecosystem is more productive and resistant to major changes.” The comparison is more than just a convenient analogy. Jackson was studying microbial communities around the world, including in the Amazon, when he realized that the ecological balance in those environments was not so different from the balance present in a healthy human gut. (One of his more counterintuitive findings is that microbial communities are more biodiverse in the American Plains than in the Amazon rain forest.)

Jackson’s work on microbial diversity caught the attention of Seed, who was already interested in the microbiome in the guts of preterm infants but who did not have a background in ecology. He sought out Jackson, and the two decided to collaborate on what they call the Preemie Microbiome Project. The Duke medical researchers and ecologists who have joined that project hope to identify which species flourish in early stages of the human microbiome, how they are influenced by the consumption of breast milk, and what role they play in critical diseases affecting infants as well as in chronic diseases that occur later in life.

“The classical view of infectious disease is that a single organism invades and produces an infection,” Seed says. “But then we found that certain diseases, like irritable bowel syndrome, seem to be caused by imbalances in the organisms that communicate with the host. So then people asked, ‘Why is this not the case for many other states of human health?’ ” Preliminary work by other groups, similarly made up of both biomedical researchers and microbial ecologists, suggests that imbalances in the microbiome might also be linked to allergies, diabetes, and obesity.

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