Harnessing the Human Microbiome

Your body is not your own. It’s also the walking, talking home of tens of trillions of bacteria, viruses, mites, and fungi, which collectively outnumber your human cells by at least 10 to 1. They help you digest your foods, metabolize your drugs, maintain your weight (or not), keep pathogens at bay—even prepare your children for their new world.

We’ve known of some of these microbes for more than a century—even suspected a few of them might be benefitting us. Not until the last decade, however, did we have the tools needed to get an honest census of exactly what our microbial shadow—our microbiome—really looked like. That shift happened when researchers realized that the DNA sequencing advances and computational techniques being used by environmental microbiologists to analyze bacterial genomes could also be applied to the human body. A few years later, in 2007, the National Institutes of Health launched the Human Microbiome Project (HMP), pouring more than $170 million into a study of nearly 250 healthy adults to create a reference snapshot of a healthy human microbial community. What the microbemapping project turned up when the study concluded this June astounded everyone.

Not only do our microbes wildly outnumber us—showing up behind our ears, between our teeth, even in our lungs—but no two populations are quite alike. In fact, more than 10,000 different microbial species may call the human body home. The microbe community between your toes differs from that on your heel, which in turn differs from your neighbor’s heel—although his may still perform many of the same functions.

“It’s been surprising,” says Ruth Ley, a microbiologist at Cornell University. “One reaction was, ‘Oh gosh, it’s so complicated, we’ll never get a handle on what’s important. Now we are starting to home in on what are actually going to be the important bits in terms of interactions with the hosts in various contexts.”

In one of her most recent studies, for instance, she tracked the transformation of women’s guts over the course of pregnancy, finding that near the end of gestation, the women’s normal microbiotic populations dropped in diversity and began favoring a pro-inflammatory microbial profile almost indistinguishable from that of a person with metabolic syndrome. Ordinarily, the changes would be dangerous—implanted into mice, the microbes caused weight gain and insulin resistance—but in a pregnancy, hypothesizes Ley, they might be helping keep the mother from rejecting the fetus while preparing her body for breastfeeding.

Pregnancy isn’t the only time these microbe populations shift. The community of intestinal helpers, easily the richest in our bodies, also evolves with age, diet, and metabolic state. Tantalizing studies hint that changes to the gut biota could have enormous implications in modern health problems like obesity. Obese mice and humans both show different gut microbe profiles than their lean counterparts, for instance, and germ-free mice given a transplant of gut microbes promptly gain weight. High-fat diets also appear to alter gastrointestinal populations in mice, favoring the animals’ ability to extract more energy from their food. What’s alarming, says microbiologist Martin Blaser of New York University, is that our overuse of antibiotics may be killing off bacteria involved in regulating key metabolic circuits, such as those using leptin and the ghrelin hunger hormone.

Scientists also suspect links between our microbiota and diseases ranging from diabetes and cancer to COPD and asthma. If these circuits can be mapped out not just in form—where the bulk of the research has focused to date—but in function, so that scientists can learn how to harness the microbes, the therapeutic potential could be revolutionary.

“We know that microbes manipulate immunity, and we know that microbes manipulate metabolism,” says Blaser. “If we could figure out the right ones, or figure out the right principles, then we may be able to treat [these disorders].”

The possibilities, he adds, are “at least equal to the potential of stem cells for changing health and disease.”

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