In Search of the Bacterial Garden of Eden

http://www.kqed.org/.stream/anon/radio/science/2013/05/2013-05-06-science.mp3

A vast and teeming crew

Here's something to stop and consider: You are mostly not you.

Ninety percent of the cells in your body don't have your DNA. They weren't in you when you were in the womb. Instead, they belong to trillions of tiny bacteria and other microbes that live in your stomach, your mouth and on your skin, among other places. Collectively, they make up between five and ten pounds of your body weight, a vast and teeming crew known as the microbiome.

Scientists have known about the microbiome for some time, but the advent of relatively inexpensive DNA sequencing has transformed the research, making it possible to sequence – and therefore identify – thousands of species of bacteria and other microbes at once.

Among those doing the cataloging is Katie Pollard, a geneticist at the Gladstone Institutes in San Francisco.

Not long ago, Pollard was chatting with a few colleagues in a weekly meeting when one of them, a grad student named Chris Gignoux, mentioned some field work he'd been doing in a remote part of South Africa with an indigenous sheep and goat herding group called the Khoisan.

The Khiosan are thought to be the oldest genetic group on earth, ancestors of the rest of us. Even their language is unique, a “click” language with consonants found nowhere else in the world.

Gignoux is part of a team trying to piece together the Khoisan's evolutionary history by studying their DNA, which the team extracts from saliva samples collected during field research trips to South Africa.

But the scientists were running into a problem. The Khoisan samples were contaminated with non-human cells: bacteria and other microbes that live in the Khoisan's mouths.

“The exact DNA that they were viewing as contamination was very interesting to us,” says Pollard.

A garden in your gut

In recent years, scientists have come to see these bacteria and other microbes as a delicate ecosystem inside each of us. You can think of it as a garden in your guts, one you are constantly tending and adding to every time you eat a meal or are exposed to something in your environment.

And just like a garden, things can get out of whack. Invasive species take over; certain plants die off.

And when this happens, scientists believe, people can get sick.

Michael Fischbach is an assistant professor in the school of pharmacy at UCSF. He reels off a list of diseases that might – repeat, might -- be connected to changes in our microbiome: “the inflammatory bowel diseases, including Crohn's disease. Possibly diabetes and obesity. Possibly even allergic diseases like asthma.”

This is new science. No one really knows. But Fischbach and others who study the microbiome are excited about the potential here, in part because of two recent discoveries.

Fecal transplants and an unlikely connection

One was the announcement last year that people suffering from a stubborn bacterial infection called C.difficile were cured after receiving fecal transplants. They ingested fresh feces – collected from healthy donors and teeming with healthy bacteria – through a tube in their nose. It was a microbiome transplant, and it worked.

The second development came last month, when a researcher at the Cleveland Clinic published results connecting bacteria in people's guts to heart disease.

“Nobody would have put heart disease on that list,” says Fischbach.

He says the announcement sent ripples of optimism throughout the microbiome research community. “The notion that you could come up with something that is going to surprise even those who have been working on it for some time is very much in the air.”

Also fueling the excitement is the recent completion of the Human Microbiome Project, an effort, funded by the National Institutes of Health, to identify and catalogue the microbiota of 242 healthy American volunteers.

Now that scientists are starting to get a handle on what kinds of microbes live in the human body and, roughly, how those populations differ from one individual to another, a key question will be whether there is such a thing as an “ideal” microbiome.

In other words, if a bad, or imbalanced microbiome can make people sick, what does a good, balanced microbiome look like? What are the microbes that have evolved to keep us healthy, and how do they do it?

Was there a microbial Garden of Eden?

This is a hard question to answer because most of us have made huge, sweeping changes to our microbiomes at least several times in our lives by taking antibiotics.

David Relman, a professor of medicine at Stanford, was one of the first scientists to use DNA sequencing to study the makeup of the microbiome, using a swab from the inside of his own cheek.

Since then, his work has explored how antibiotics affect the microbiome, and how long those changes persist. He says while antibiotics have saved millions of lives, they’re a blunt instrument.

“In the past, we thought of antibiotics as magic bullets,” Relman says. “But – I hate using the military metaphor – they're more like a cluster bomb, or a neutron bomb. They're indiscriminate. And there's a lot of collateral damage.”

That collateral damage includes healthy bacteria, which may play important roles in digestion and other functions. Antibiotics can also create ideal environments for harmful bacteria to thrive.

Sometimes, the balance restores itself. Other times, the changes may be permanent. If a particular strain of bacteria is lost, it can't be passed on from one human generation to the next.

But this is hard to study. Because there’s almost no one out there who hasn't taken antibiotics. Which brings us back to the Khoisan.

Learning from the Khoisan

What occurred to Katie Pollard is that the Khoisan for the most part haven’t had that repeated antibiotic exposure. If researchers can find bacteria in the Khoisan that don’t show up in the saliva of industrialized groups, she says, “that would suggest that something in the modern lifestyle has potentially wiped out these bacteria.”

This work is just beginning. So far, Pollard's team has identified about 900 species of microbes in the Khoisan saliva. Next, they'll compare those species to samples from other populations to see whether there are any completely novel microbes in the Khoisan, microbes she and others haven't seen before.

Lest anyone start thinking that the Khoisan microbiome could be some sort of wholesale solution to modern ills (maybe imported through some kind of trans-Atlantic fecal transplant?) think again.

Among those 900 bacterial species identified, says Pollard, are several that you definitely wouldn't want, a fact that becomes clear when you look at photos of the Khoisan, many of whom are missing teeth.

“Many of the bacteria we've found are known pathogens,” says Pollard, “in terms of gum disease or enhancing plaque.”

Modern medicine has not been all bad for the microbiome.

Pollard and others who do DNA sequencing on gut microbes face a massive computational challenge, one that makes the human genome project look like a cakewalk.

But the end result, say Pollard and others, could be new insights into how we could tweak, even curate the bacteria in our bodies, to make ourselves healthier.