Beyond the gut: unlocking the secrets of the microbiome

Alzheimer's disease researcher Myles Minter, PhD, still sounds a little surprised while describing the improbable group of researchers he is collaborating with these days - not just neuroscientists but also colleagues from fields as disparate as gastroenterology and marine biology.

Minter and his advisor, Sangram Sisodia, PhD, the Thomas Reynolds Sr. Family Professor of Neurosciences, wanted to take their Alzheimer's research in an unexpected direction, exploring the link between bacteria in the digestive system and brain health. The resulting study, published in July in Scientific Reports, broke new ground. It showed that a long-term course of antibiotics in mice weakened some of the telltale symptoms of Alzheimer's disease in the brain, while at the same time producing marked changes in the makeup of their gut bacteria.

"I've been working with marine biologists who go deep-sea diving and take samples," said Minter, a postdoctoral scholar in neurobiology, shaking his head. "Yes, previously I definitely would laugh at it, but once you put ideas together from different fields that largely have been believed to be segregated from one another, the possibilities are really amazing."

This research marks one of the first collaborations coming out of the Microbiome Center, a joint effort by the University of Chicago, the Marine Biological Laboratory (MBL) and Argonne National Laboratory to support scientists at all three institutions who are developing new applications and tools to understand and harness the capabilities of microbial systems across different fields.

The term "microbiome" is shorthand for the vast and still largely unexplored world of bacteria, viruses, fungi and other microorganisms that inhabit every corner of the planet. To put it simply, they're everywhere. They're in the air, water and soil. Commensal bacteria live side by side with our own cells on our skin, in our mouths and along our airways. The bacteria that live in us also colonize all the surfaces we interact with, including our homes, offices and hospitals. Perhaps most important to human health, microbes in the gut constitute what some researchers consider a separate organ that shapes our metabolism, susceptibility to allergies and even responses to medical treatments.

Scientists in fields as diverse as microbiology, physics, chemistry and medicine are just beginning to understand how these ecosystems of microbes interact with each other and influence their environments. Until recently, researchers largely worked within their own disciplines, but as new technologies such as large-scale genetic sequencing and analysis have become more accessible and the momentum behind microbiome research builds, so have the opportunities for scientific serendipity.

"We're starting to find that we have a unique ability-through the microbiome-to control how environments work and maybe even use the bacteria as a method of tracking those environmental changes," said Jack Gilbert, PhD, faculty director of the Microbiome Center, as he and a group of like-minded scientists called for a concerted national effort to coordinate microbiome research across disciplines in the fall of 2015. "So we're at a point now where if we coordinate our activities as a community, we can go after the really big questions."

The scientists' call to action eventually resulted in the White House Office of Science and Technology Policy launching its National Microbiome Initiative in May 2016 to bring together public and private entities to coordinate and fund microbiome research. The new Microbiome Center is one of the first models of how research institutions can leverage existing affiliations and pool intellectual horsepower across disparate fields.

Gilbert's collection of titles speaks to the scope and ambition of the center: group leader in microbial ecology at Argonne, senior fellow at MBL, and his most unlikely appointment, professor of surgery at UChicago. He started his career as an entomologist studying butterflies before becoming a microbial ecologist (and is a fellow of the Field Museum). His work on the Hospital Microbiome Project, in which he and his team tracked the development of the microbial ecosystem in the University of Chicago Medicine's new Center for Care and Discovery as it opened in 2013, led to a collaboration with John Alverdy, MD, the Sara and Harold Lincoln Thompson Professor of Surgery, who is working to prevent infections after surgery.

"It's really bizarre. But here I am sitting in my office in the Department of Surgery, so I guess it is real," Gilbert said. "I've been in environmental microbial ecology my entire life, and then suddenly over the last five years I've started to apply the same approaches to explore the human body as an ecosystem."

So far, much of the attention on microbiome research, understandably, has centered on the digestive system and its contribution to conditions like inflammatory bowel disease or the onset of food allergies. But researchers across UChicago are already turning up evidence of the microbiome's effects in new, unexpected places.

Read more about these unexpected collaborations, published previously on Science Life:

The "second brain"

Minter and Sisodia are exploring new territory in how the gut influences brain health. They teamed with microbiome researchers to study what effect, if any, changing the bacteria in the digestive system could have on symptoms of Alzheimer's disease.

Community matters

Marisa Alegre, MD, PhD, and her team are studying the role microbiota play in the body's ability to accept transplanted skin and other organs. In a recent study, the researchers demonstrated that skin grafts in mice treated with antibiotics prior to transplantation survive longer.

An unexpected ally

Thomas Gajewski, MD, PhD, and his team produced one of the first studies to show how differences in the gut microbiome could impact the effectiveness of cancer treatment.

An ecosystem of research

To microbiologists, the idea that there is a vast world of microbes out there, living in just about any nook and cranny you can think of, isn't all that earth-shattering.

"If there is a carbon source out there, there is an organism that's going to gure out a way to make a living off it," said Dionysios Antonopoulos, PhD, a microbial systems biologist at Argonne and assistant professor of medicine at UChicago. He started his career studying the microbiology of ruminant digestive systems - i.e., cow guts - and has since moved on to studying the broader ecosystems these microbes inhabit and the give and take with resources that makes those communities stable.

To him, the interesting leap is when scientists start to take what they've learned about those other systems, from cow guts to waterways to man-made buildings, and apply it to human health.

"We're not really in complete control of our bodies; these millions and millions of other entities are influencing the way our bodies function," he said. "It's that sort of work that's sort of captured the imagination."

For Gilbert, the secret to maintaining that momentum lies in breaking down barriers between different disciplines to create an ecosystem of shared research, so that a postdoc studying Alzheimer's disease - such as Minter - may find himself learning sampling techniques from a marine biologist.

"We want to be able to break down boundaries between disciplines and institutions so that they are essentially nonexistent," Gilbert said. "Yes, individual institutes have their own research agendas. But when people talk about the Microbiome Center, they won't say the Microbiome Center at UChicago or the Microbiome Center at Argonne. They will just say the Microbiome Center."

This article was originally published in the Fall 2016 edition of Medicine on the Midway, our premier publication for friends, alumni and faculty of the University of Chicago Medicine, the University of Chicago Division of Biological Sciences and the Pritzker School of Medicine.