Lora Hooper and Rob Knight have applied an ecological approach to studying the human gut.

Sea of Microbes

Martin Blaser, a doctor of infectious diseases and chair of medicine at New York University Langone Medical Center, thinks there’s already a disturbance going on in human guts that’s not unlike the disappearance of wolves from Yellowstone. From early human history until the 20th century, Blaser says, a bacterium called Helicobacter pylori was universal.

“You can actually trace human migration by looking at variations in Helicobacter,” he says. Today, Helicobacter is still ubiquitous in developing countries around the world. In the United States, though, fewer than 6 percent of children have Helicobacter in their mix of gut bacteria. And in a series of recent studies, Blaser showed that children lacking Helicobacter are more likely than their peers to develop child-onset asthma. While the presence of Helicobacter predisposes people to ulcers, he thinks the disappearance of the microbe could explain not only rising rates of asthma but also allergies and obesity.

“We evolved in this sea of microbes, and now we’re living as germ-free as we can,” agrees Brett Finlay, an HHMI international research scholar at the University of British Columbia. “It’s a major light going on right now, that this could have consequences.”

Blaser says microbiota research is at the cusp of a scientific revolution and touching medicine at all its edges. “It’s permeating so many different fields,” he says. “In my role in medicine, I talk to nephrologists about the link to kidney disease; I talk to oncologists about the link to cancers. And I think we’re going to keep finding new links to diseases.”

One disease increasingly linked to the makeup of the gut microbiota: colitis, an inflammation of the colon. Tom Schmidt, a microbial ecologist at Michigan State University, is collaborating with doctors at the University of Chicago to study this connection when it comes to one particular form of colitis.

When doctors remove someone’s colon—because of infection, weak spots, or cancer—they replace it with a new colon, built from other nearby tissue. At first, this pouch is void of bacteria. Gradually, a microbial community develops. But in almost half of all pouches, symptoms of colitis develop. So Schmidt and his collaborators are following patients with new colons and tracking the development of the microbiota in each case. They hope to discover how the intestinal flora keeps some colons healthy and others prone to infection and inflammation.

Schmidt, like Knight, comes at the microbiota with an ecology background. His expertise is in soil ecology, and soil has surprising similarities to the gut, he says. Both environments are low in oxygen. So the techniques he developed to cultivate organisms that thrive in low-oxygen soil he can now apply to the gut. And the big question that Schmidt hopes to answer resonates with both environments.

“It’s a fundamental ecological question: how resilient is this community?” says Schmidt. “In soil, we look at what happens after you change the land from agriculture to abandoned, or from grassland to agriculture. In the gut, we look at what happens after a course of antibiotics, or in a new colon. How quickly can the community recover to its previous state? Does it recover at all?”

Finlay, at the University of British Columbia, has some of the same questions. He wants to know how antibiotics change the bacterial community in the gut and how this shift can lead to, or prevent, disease. He uses techniques similar to Knight’s to get a snapshot of a mouse’s microbiome. Then he gives the mouse an antibiotic and takes a new snapshot. One study, by another lab group, showed that pretreating mice with antibiotics shifted their gut microbes so that they became resistant to Salmonella infection. Other findings, by Finlay and his colleagues, suggest that shifts in the microbiota caused by different antibiotics can weaken the immune system.

“When researchers compare mice with different degrees of susceptibility to disease, they’ve always searched the mouse genes for the explanation and not found much,” Finlay says. “Now we’re learning that’s because the difference isn’t in the mouse genes, it’s in the microbiota.”

Hooper: Amy Gutierrez / AP ©HHMI, Knight: Carmel Zucker

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