February 23, 2015

Alexa Weingarden

Alexa Weingarden

Doctoral Dissertation Fellow

Exploring How Gut Microbes Affect Our Health

Most of us don't think about the myriad microorganisms living in harmony in our guts – until something upsets this delicate balance, causing bacteria to grow out of control and make us sick.

Affecting more than half a million people in the U.S. each year and causing about 15,000 annual deaths, Clostridium difficile (C. difficile) infection has become an increasingly severe health problem. Symptoms range from diarrhea to serious intestinal damage; most at-risk are patients taking antibiotics and the elderly. The currently recommended antibiotic treatment for C. difficile is often ineffective, with the infection returning in about 20 percent of patients.

Fortunately, PhD candidate Alexa Weingarden has a passion for understanding current treatments for the infection, and for designing new ways to treat it.

"I've been interested in studying how gut microbes affect human health since undergrad," she says. "The opportunity to pursue that kind of research while directly improving treatments for patients is perfect for me."

Transplanting feces from healthy individuals into the colons of patients suffering with C. difficile is the most successful known treatment, curing the infection over 90 percent of the time. However, it's still unclear how the transplants, which change fecal microbiota in patients to resemble donor microbiota, eliminate the infection.

Weingarden's research focuses on understanding how fecal transplants work and why they are so effective in curing the infection through applying techniques that characterize the state of the fecal microbiome before and after transplants.

Using that knowledge, she designs new, alternative ways to treat the infection for patients who can't have or don't want the transplant.

Weingarden's work sheds light on the relationships between pathogens, native gut microbes, and the human host.  Evidence has linked gut microbes with issues ranging from inflammatory bowel disease to diabetes to autism, making fecal transplants a possibility for some of these diseases. "Understanding how fecal transplants work is integral to investigating whether they can be used for other diseases," she says.

Weingarden has found that fecal microbiota transplantation restores normal bile acid metabolism, which is important in curing Clostridium difficile. "This discovery paves the way for the development of novel therapeutics for this important problem," says physician-scientist Alexander Khoruts, her co-advisor.  "Her work is the epitome of translational science and provides a fundamental understanding of the dysbiosis caused by unbalanced gut microbiota," adds microbiologist Michael Sadowsky, her co-advisor.

A Twin Cities native, Weingarden attended Harvard during her undergraduate years, studying Biology and Earth & Planetary Sciences. She returned to Minnesota in 2009 to study Microbiology, Immunology, and Cancer Biology through the University of Minnesota's MD/PhD Medical Scientist Training Program. "The program is very strong, and my graduate program is recognized nationally," she says. "I felt the training I received here would allow me to succeed after my education is completed." 

As a 2014-15 Doctoral Dissertation Fellow, Weingarden has opportunities to communicate her research to a general audience, a skill she considers critical for scientists. "Figuring out how to present my work to a non-science audience helps me focus on what's really important about my research and realize where the biggest gaps are," she says.  She also received the Graduate School's Interdisciplinary Doctoral Fellowship in 2012-13, and has been involved in student admissions. Outside of her academic activities and accomplishments, she studies classical voice and has acted in several Twin Cities community theater productions. 

Weingarden credits her advisors with providing essential knowledge of microbiology, human biology and transplants. "They're both committed to helping me grow as a researcher and as a physician, and to ensuring that I'll continue to succeed after I've moved on to the next stage of my training," she says.

After receiving her PhD, Weingarden will spend two more years in medical school. She then plans to enter a research-focused residency in Internal Medicine and complete a fellowship in Gastroenterology. Eventually, she hopes to run her own research lab and become a leader in the field of human microbiome studies.

Learn more about the research of Doctoral Dissertation Fellows at the 2015 Doctoral Research Showcase >

-Lyra Fontaine