Virginia Tech Carilion School of Medicine student Miranda Creasey’s research into the microbiome (gut bacteria that have been linked to genetics and neurodevelopment) may contribute to a better understanding of what leads to the development of conditions like autism.

The fourth-year medical student began working in the Neurotrauma Research Lab of Michelle Theus, associate professor of biomedical sciences and pathobiology at the Virginia-Maryland College of Veterinary Medicine and associate professor of health sciences and co-director of the university’s Translational Biology Medicine and Health Graduate Program, as an undergraduate at Virginia Tech.

After graduating with degrees in human nutrition, foods, and exercise and psychology, Creasey worked in the lab the year before she began her studies at VTCSOM and started the microbiome project she would continue the next four years as a medical student. Being able to continue working in the lab and have Theus as her research mentor was a big reason Creasey chose VTCSOM.

“The microbiome world encapsulates a wide spectrum of functions that can be attributed to many varieties of disorders and conditions,” Creasey said. “My study isn’t about autism, per se, but rather about observable changes in behavior that can be correlated with certain aspects of brain development, and these changes may be related to the microbiome.”

The microbiome consists of a number of living organisms, such as bacteria, viruses, archaea, and fungi. Creasey’s first part of the project was to deplete the bacteria in the guts of lab mice and their offspring. In doing so, she observed social deficits in the mice sharing some features similar to those observed in people with autism. The mice kept to themselves and were socially distant from other mice.

In addition to observing the behavior of mice who had altered microbiomes, Creasey’s research also observed dysfunctional microglial cells in the affected mice. Microglia are the brain’s immune cells that destroy harmful debris and play an important role in shaping synaptic connections between neurons during brain development.

The mice without the bacteria in their gut and who had shown social deficits carried abnormally functioning microglia. One job of the microglia is to “prune away” an overabundance of initially produced synaptic connections, which allows the brain to function more efficiently.

“Individuals with autism have been shown to retain too many of these connections, which may explain why our mice seem to exhibit an autism-like phenotype,” Creasey said.

The next part of the project involved administering a novel strain of lactobacillus to the mice who had bacteria-depleted guts. Interestingly, the bacteria were able to restore their behavior and return their microglia back to normal function.

“That’s the direct connection between the gut and the brain,” Creasey said. “So, we have solidly established the connection, but we don’t know exactly how it works.”

In the final phase of her project, Creasey is trying to answer that question by using computational modeling to identify the distinct metabolic makeup of the novel lactobacillus strain and how its metabolism may promote changes in neurodevelopment. Using the genetic material of the novel strain of lactobacillus and comparing it to a representative strain, Creasey hopes to build metabolic networks specific to each strain to determine their specific differences.

Ultimately, Creasey’s research may point to the efficacy of using the novel lactobacillus strain to help people who have issues with social deficits.

Creasey is quick to acknowledge the researchers she has worked with on this project, including Yeonwoo Lebovitz, alum of the university’s translational biology, medicine, and health graduate program; Bronson Weston, graduate student in genetics, bioinformatics, and computational biology; and her mentor, who she has worked with for nine years, starting with the day she walked into the Theus lab as an undergraduate looking to shadow someone.

“It’s wonderful to cultivate relationships with mentees that last as long as ours has,” Theus said. “Miranda is bright, kindhearted, and mature. I greatly appreciate her friendship and will very much enjoy watching her take on the next leg of her journey.”

Creasey plans to pursue pediatric neurology.

“Dr. Theus is a force to be reckoned with,” she said. “Even when I venture off into areas that are foreign to me and a little intimidating, the whole lab, especially Dr. Theus, encourages me to jump right in and learn by doing. I’ve never felt like I was a nuisance.”

In fact, due to her positive experiences in the Theus lab, Creasey considered earning a Ph.D. rather than an M.D.

“But my desire to work with patients was just a little stronger, so I ended up in medical school,” she said.

Creasey has been an author on several publications during the various legs of this project, including those published in the journals, Brain Behavior and Immunity and Neuroscience Reviews. She plans to continue with biomedical research after she graduates and moves into residency.

“One of the reasons I hope to continue doing research as a clinician is that it helps me to view my patients in a much more complete and well-rounded way,” she said. “It draws me out of the box of linear thinking and helps me form questions that I wouldn’t otherwise.”

The Virginia Tech Carilion School of Medicine is one of only a few medical schools in the country that requires students to complete a rigorous, multiyear research project as part of their curriculum. This dedicated element of the school’s curriculum has led to its rapidly growing reputation for training exceptional scientist physicians. Since 2014, students have given more than 375 research presentations at regional, national, and international meetings. In addition, there have been 112 research publications with Virginia Tech Carilion School of Medicine students as authors and co-authors.

As a Letter of Distinction recipient, Creasey is one of eight students in the class of 2021 who will give an oral presentation about their research during the school’s Medical Student Research Symposium on March 26 starting at noon. Other members of the class will present poster sessions of their work in break-out sessions.

In accordance with COVID-19 safety precautions, in-person attendance to the event is limited to the Class of 2021 and select faculty members, though other guests are encouraged to register and attend virtually.