by Kate Dohner
“When you go to the forest, what do you see?” asks A. Murat Eren, whom everyone calls Meren.
While the trees are the most noticeable, it’s important to pay attention to what’s on the forest floor—shrubs, wildflowers, ferns, and mosses. Without them, Meren points out, there would be no forest at all.
Like the forest, the human gut contains a multitude of organisms—bacteria, fungi, and viruses—collectively known as the human microbiome.
‘If you can observe a forest after a fire, you can see how it renews,” Meren said. “It all starts on the forest floor, led by ‘pioneer’ species like grasses and shrubs.”
Similarly, Meren is studying the human microbiome after a period of disturbance to see which bacteria help return it to a healthy state.
For instance, when the balance of bacteria in the gut is disrupted, a bacterium called Clostridium difficile or C. diff can proliferate. While C. diff sometimes responds well to antibiotics, recurrent, resilient infections are not uncommon. In these instances, patients can benefit from fecal microbiota transplantation or FMT, the transfer of “good bacteria” from a donor’s stool to a recipient. Although FMT is successful in many cases, there are risks, including the unintentional transfer of problematic biological material, such as viruses.
“With FMT today, we essentially gather the entire contents of a healthy forest and dump that ecosystem into a disturbed forest,” Meren explained. “Though that may work, we don’t know how.”
Meren and his team are on the hunt for the specific bacteria that can set up a healthy environment in any distressed digestive system, especially for those battling inflammatory bowel diseases.
“The microbes we’re looking for are like the person who can talk to anyone at a party,” Meren said. “She’s happy anywhere and helps put others at ease.”
Collaborating with world-renowned clinical experts (including Thomas Louie and David Rubin), Meren and his team are studying fecal samples from people around the world to identify these versatile microbes. Using the advanced computational tools they develop, Meren’s team can compare and categorize bacteria found in a variety of people—from infants to adults, to those in industrialized countries versus places like Tanzania.
The goal is to not only advance our understanding of the trillions of bacteria that make up the human microbiome, but to track down the special characters that can make any microbial community thrive.
“We scientists often gravitate toward what is most abundant in an environment—a byproduct of our historical relationship with numbers and the methods we have to make sense of them,” Meren said. “As a trained computer scientist, I recognize that bias and always remind myself that function—how something contributes to its environment—is what we’re really after.”
Meren cites the role of police in society; though they make up a small proportion of the population, they are critically important to how communities function. So it may be with certain bacteria.
“Instead of investigating just any bacteria we find in healthy human guts, we are conducting a systematic study to find microbes that can help microbial ecosystems recover from distress,” Meren said.
The team has already identified some “microbial peacekeepers” and are continuing their search for more, building a comprehensive genomic and culture library to see how each microbe behaves in different experimental settings.
Ultimately, Meren hopes this work will lead to a targeted, reliable microbial therapeutic that will not only help those with C. diff infections, but also people with inflammatory bowel disease and other gastrointestinal problems.
“Although basic science is demanding and even frustrating at times, important insights will only emerge from this type of work. My group and I believe we are on the right track to finding the critical members that keep the microbial forest in our guts healthy.”
“There’s so much more to learn,” added Meren, “but here at the University of Chicago, we have the right tools to recognize and investigate fundamental questions and are surrounded by tremendous expertise in immunology, microbiology, and gastroenterology—collectively offering us a rare opportunity to transform medicine.”
Kate Dohner is a senior writer for the University of Chicago Medicine & Biological Sciences Development office.