Technological Advances Powering New Insights into the Human Microbiome

This is the first article in a series about research related to the human microbiome at Partners’ academic institutions. We talk to Lynn Bry, MD, PhD, from the Department of Pathology at Brigham and Women’s Hospital.

If you think about it, the scientific quest to understand the human microbiome is not unlike trying to follow along with HBO’s hit TV series “Game of Thrones.”

The show features intricate plotlines and a wide and complex cast of characters who interact in a myriad of ways—sometimes working together, sometimes at odds with each other. The lines between the heroes and villains are frequently blurred, and at any moment, a sudden 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 revealed 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 C. difficile, the stakes can literally be life or death.

Researchers in the academic medical institutions of Partners HealthCare are using a variety of innovative strategies to learn more about how the microbiome works and what happens 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 brand-new area of scientific investigation. In fact, research into the differences between colonies of microbiota in humans dates back to the late 1600s.

Dr. Bry , Director of the Host Microbiome Center at BWH, says recent breakthroughs include the introduction of technologies such as next generation sequencing and high throughput proteomic mass spectrometry. These tools have provided researchers with unprecedented insights into the composition of microbes at the genetic level.

The technologies also make it possible for researchers to observe how an individual’s microbiome changes over time and how it reacts to different perturbations.

“We can now distill a complex ecosystem into a subset of component microbes we think are important,” Bry says, “and then go back to experimental systems to understand the dynamic and what’s truly driving what in the system.”

For Bry, who has been studying interactions between microbes and the cells of the human intestine since the 1990s, these breakthroughs helped inform new approaches to identifying what goes wrong in conditions such as treatment-resistant C. difficile, inflammatory bowel disease, food allergies and more.

Seeking New Solutions 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’s particularly harsh on patients over the age of 65, especially those in hospitals and nursing home settings. A 2015 research study estimated that the cost of treating the condition is $6.3 billion per year.

C. difficile is an infection caused by the pathogenic bacteria Clostridium difficile that results in inflammation of the intestines and severe diarrhea. Patients taking antibiotics for other conditions are most susceptible as they can alter the balance of microorganisms in the body, which creates opportunities for C. difficile to attack.

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.

According to the CDC, one in 11 patients aged 65+ will die within a month of receiving a C. difficile diagnosis, and 80 percent of all C. difficile-related deaths come from the patients in this age group.

At BWH, Bry is part of a precision medicine project seeking 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 resolve.

“It’s the combination of having the experimental system with the high throughput platform, the computational algorithms, the back and forth between what you are able to learn at the bench with what you’re able to learn in silico,” Bry explains. “Certainly, we’ve had the best success when we compare [our results] to the patient population.”

“We need to understand what is out of balance and then understand what we can do about it.”

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 plot twists on “Game of Thrones,” the more researchers learn about the microbiome, the more questions are sure to arise.