If you think about it, the scientific quest to understand the human microbiome is like trying to keep up with HBO’s hit TV series “Game of Thrones.”
The show features intricate plot lines and a complex cast of characters who interact in myriad ways—sometimes working together, sometimes at odds.
The lines between the heroes and villains are frequently blurred, and at any moment, a unexpected event can throw everything into chaos.
While it may lack the swordplay and special effects, the study of the microbiome—the interactions between humans and the trillions of microorganisms that live on and within our bodies—has its own web of complex relationships and ever-shifting power balances.
In many cases, the microbiota in our bodies play a crucial role in keeping us healthy, assisting with everything from digestion to ensuring our immune system operates effectively.
In other cases, however, they can be harmful.
Imbalances or disturbances in the microbiome can lead to food allergies, infections, and chronic inflammatory conditions, and when it comes to conditions such as treatment-resistant C. difficile, the stakes can literally be life or death.
Researchers within the academic medical institutions of Mass General Brigham are taking advantage of recent technological breakthroughs learn more about how the microbiome works and how it changes in different disease states.
It’s a massive undertaking with the potential to make a major impact on patient care.
The Technological Push
Given all the attention it has received in recent years, it may seem like the microbiome is a new area of scientific investigation. But the study of differences between colonies of microbiota in humans dates back to the late 1600s.
Lynn Bry, MD, PhD, Director of the Host Microbiome Center at Brigham and Women’s Hospital (BWH), says recent technological breakthroughs such as next generation sequencing and high throughput proteomic mass spectrometry have provided researchers with unprecedented insights into the composition and function of microbes at the genetic level.
The technologies also show how an individual’s microbiome changes over time and how it reacts to different perturbations, such treatment-resistant C. difficile, inflammatory bowel disease, food allergies and more.
“We can now distill a complex ecosystem into a subset of component microbes we think are important,” she says. “Then we can go back to experimental systems to understand what’s truly driving what in the system.”
Seeking New Strategies for C. Difficile
Bry and her team are particularly interested in learning the mechanisms behind treatment-resistant C. difficile, a potentially life-threatening infection that that often impacts patients over the age of 65, especially those in hospitals and nursing home settings.
A 2015 research study estimated the cost of treating the condition at $6.3 billion per year.
C. difficile is an infection caused by the pathogenic bacteria Clostridium difficile, which results in the inflammation of the intestinal tract and severe diarrhea.
According to the Centers for Disease Control and Prevention (CDC), there are 500,000 cases of C. difficile contracted in the United States each year, and the infection becomes recurrent in about 20 percent of those patients, which can lead to frequent and debilitating attacks.
Patients who are taking antibiotics for other conditions are most susceptible to infection, as antibiotics can alter the composition of the gut microbiome and create opportunities for C. difficile to attack.
At BWH, Bry is part of a project that is using precision medicine techniques to identify biomarkers that indicate which patients are at greater risk of recurrent C. difficile infections and why.
It’s a problem that will likely take many different tools to solve.
“It’s a combination of experimental systems with high throughput platforms, computational algorithms, and moving back and forth between what you are able to learn at the bench and what you’re able to learn in silico,” Bry explains. “Certainly, we’ve had the best success when we compare our lab results to the patient population.”
Bry hopes that research into C. difficile and other areas of the microbiome will lead to a new range of treatment options for patients.
This could include changes in diet, ingestion of modified microorganisms (so-called “bugs with drugs”), and the development of new molecular therapeutics, among others.
Industry partnerships will play a key role in developing these therapies and bringing them to market, she adds.
“We know we are not optimally positioned to commercialize [new therapeutics], so we would certainly want to forge collaborations with industry to make use of them, get clinical trials going and see what we can use in the clinic.”
And just like the many unexpected developments in “Game of Thrones,” the more researchers like Bry learn about the microbiome, the more plot twists are sure to arise.
Brian Burns 