Looking closer at role of microbiome

Jack Gilbert and colleagues study bacteria’s broad influence

Editor’s note: This story is adapted from the July/August 2015 issue of The University of Chicago Magazine. Read it in its entirety here.

There’s a story that Assoc. Prof. Jack Gilbert, a microbial ecologist at UChicago and Argonne National Laboratory, likes to tell about a bacterium called Enterococcus faecalis. It’s sort of a love story gone wrong.

Squat and vaguely jellybean-like, measuring about three microns long, E. faecalis lives in the human gastrointestinal tract. Under normal circumstances, the relationship is friendly. It’s close. It’s what microbiologists call commensal, a term whose Latin etymology conjures up togetherness and a shared dinner table.

“In its original state, just living inside your gut, this bug is totally harmless,” Gilbert says. “In fact, it’s beneficial. It helps train your immune system.” Your body wants it there, needs it there, has evolved to live with it. “It’s a natural part of your gut’s flora, your ecosystem.”

All that can change, though, when a person goes in for gastrointestinal surgery. Like, for instance, to remove part of the colon and stitch the remaining pieces back together, a routine treatment for colon cancer. Afterward, some patients develop what’s called an anastomotic leak. The seam where the bowel has been rejoined breaks open, and fluids from the intestine begin seeping into the body. It’s a rare complication, but it can be disastrous, sometimes fatal. Even after years of increasingly better materials—glues, staples, stronger stitches—and increasingly precise surgical techniques, anastomotic leak persists. Some surgeons opt to avoid the risk altogether by performing a colostomy that, unpleasantly, diverts fecal matter into an external bag.

The culprit, it turns out, is usually not the stitches or the surgeon; instead, it’s a particular strain of the otherwise commensal E. faecalis. In a study published this past May, Gilbert and John Alverdy, the Sara and Harold Lincoln Thompson Professor of Surgery, found that the bacterium creates small holes in the intestine at the surgical site, degrading the tissue and weakening the connection. In rats with anastomotic leaks, the abundance of E. faecalis ballooned 500-fold. “It becomes like a swarm of locusts,” Gilbert says of the microbe. “And it swarms directly to the site of damage in the cell wall, grabs hold of it, and starts to break down the collagen that the body is trying to use to repair the cell damage. It’s like going to the scaffolding on a new building and just ripping it apart. And the building falls down.”

But why? What makes this friendly bug turn against its host? The answer, Gilbert says, underlines an increasingly inescapable need to reimagine the way medicine is practiced. Not just surgery, but all medicine. And—now that he’s talking about it—not just medicine, but modern life more broadly. The cities we build, the buildings we work in, the food we eat, the homes we keep, the environments where we live our lives and raise our children. All these factors affect the microbes living inside us, which in turn, scientists are discovering, can influence everything from obesity to Alzheimer’s to asthma.

Unraveling influence of microbiome

Humans are vastly outnumbered in their own bodies. For every human cell, there are 10 cells of bacteria. But until they’re born, babies are sterile. They leave the womb and pass through the birth canal, where they’re colonized by their mothers’ microbiota. After that, children pick up bacteria everywhere they go: from their parents and siblings and other people, from pets, food, clothes, floors, furniture, toys, plants, trees, dirt, and the air all around them. By the time children learn to walk, they’re enveloped, inside and out, by a massive, invisible kaleidoscope of microorganisms, 100 trillion or so. Those microbes—mostly bacteria but also some viruses and fungi—live in our mouths and blanket our skin; they congregate in our nasal passages and ear canals and on the surface of our eyes. More than anywhere else, they inhabit our digestive systems.

Taken together, these organisms are called the microbiome, and they are so pivotal to our health, both its function and dysfunction, that scientists have begun thinking of them as another organ. Indeed, about three pounds of every person’s biomass is microbial; that’s roughly the same weight as the human brain. Friendly microbes living happily in our bodies help train our immune system, help digest our food and absorb nutrients from it, and help keep pathogens at bay. But the role that E. faecalis plays in anastomotic leaks is only one example of what can happen when this complex and dynamic community of organisms falls out of balance.

UChicago scientists, including Gilbert, are researching the ways in which “dysbiosis,” a microbial imbalance inside the body, can lead to food allergies and inflammatory bowel disorders. Pathologist Alexander Chervonsky studies the link between an absence of certain microbes in the gut and the onset of type 1 diabetes and other autoimmune disorders. He’s also examining how the differing composition of male and female microbiomes may at least partly explain why autoimmune disorders strike women more often than men. Pediatrician Stacy Kahn has looked at how fecal transplants, which transfer gut microbes from one person to another, can be used to treat recurrent Clostridium difficile infections in children.

Geneticist Carole Ober is working to unravel the microbial influence on asthma. For decades, Ober has studied the Hutterites of South Dakota and the Amish of northern Indiana, two groups with nearly identical genetic ancestry—both are Anabaptists who live on communal farms—but strikingly divergent childhood asthma rates. At 15 percent, the Hutterites’ rate exceeds the national average, while the Amish Ober studies have almost no asthma at all. Her recent research points to the seemingly protective effects of dust, and the microbes within it, found in Amish homes. New research, not yet published, on which Gilbert is a collaborator, also points, he says, to differing traditional practices that have Amish children working out in the barns at a much earlier age than the Hutterite children.

Some of the most promising discoveries have come in the realm of allergies. Particularly food allergies—peanuts, tree nuts, fish, shellfish, milk, eggs, wheat, and soy are the big ones—which have risen dramatically, and somewhat mysteriously, over the past two decades. Last year, UChicago immunologist Cathryn Nagler, the Bunning Food Allergy Professor, identified a particular class of gut bacteria, Clostridia, that seems to protect the body against allergies by preventing allergens from getting into the bloodstream.

Limitless research potential

Microbiome research is still in its early stages. A decade or more ago, genetics seemed like the key to understanding our biological fates. Find the gene and you’ll find the disease. But the picture turns out to be much more complicated. Genes are important, but not by themselves determinative. And the same DNA-sequencing technology that made possible the map of the human genome also made it possible to sequence and analyze the microbes in the human body. A whole new universe sprang into view.

The promise seems so limitless. At a panel discussion on the microbiome during Alumni Weekend, Gilbert cautioned people not to get ahead of the science. “We can’t go in thinking this is the answer to everything.” So little is known, and the complexity is almost unimaginably vast. Mouse models are a long way from human clinical trials.

Still. Alverdy, who collaborated with Gilbert on the E. faecalis study and has spent more than 20 years analyzing the behavior of intestinal bacteria, says this research is perhaps the most significant happening now. “I believe that understanding the microbes is how we’re going to save the earth,” he says. “Really. Truly. They’re that important.”