John Moore’s Research Screens for Patients’ Vulnerability to Antibiotic-Associated Diarrhea

New Rapid Screening Tool Assesses Gut Microbiome’s Susceptibility to Infection

The human health advances following the discovery and large-scale manufacture of antibiotics cannot be overstated. These wonder drugs have allowed health professionals to control a wide variety of communicable diseases caused by bacteria, from global health threats such as malaria, to more readily treatable infections such as cholera and pneumonia. When administered before surgery, antibiotics can prevent bacterial infection from occurring, speeding patients’ recovery time.

Like many drugs, antibiotics can cause unwelcome and potentially dangerous side effects. Agencies such as the Centers for Disease Control and Prevention and the National Institutes of Health constantly look for novel approaches to improve patient outcomes. More specifically, these agencies fund research to protect and restore the body’s naturally occurring bacteria, called the microbiome, before and after taking antibiotics.

John Moore, a University of Virginia Ph.D. student in electrical engineering and 2019 UVA Global Infectious Diseases Institute Fellow, has developed a diagnostic tool to meet this challenge.

Guided by his academic adviser Nathan Swami, professor in UVA’s Charles L. Brown Department of Electrical and Computer Engineering, and co-advised by Dr. Cirle Warren, a clinical infectious disease specialist with UVA Health, Moore developed a tool to rapidly assess the microbiome’s susceptibility to clostridium difficile (C. diff) infection. C. diff is the primary cause of antibiotic-associated diarrhea and colitis, leading to about 500,000 illnesses each year, according to information published by MedLine Plus, an online health information service of the National Library of Medicine.

Antibiotics upset the balance of good and bad bacteria in the gut’s microbiome, setting conditions for C. diff endospores to germinate and attack the lining of the intestine. Existing methods of metabolomic analysis to assess susceptibility to C. diff infection are expensive and time-consuming, and provide only a partial picture of the complex interactions within the gut.

Moore developed a more accurate and rapid way to measure spore generation within fecal metabolites, which are the final product of cellular and microbial metabolism in the human intestinal tract. In addition to the fellowship from UVA’s Global Infectious Diseases Institute, a grant from the National Institutes of Health supports this exploratory or developmental research.

Moore has worked to prevent C. diff infection for a number of years. From 2012 through 2015, he was a research specialist in infectious diseases in Warren’s laboratory in UVA Health’s division of infectious diseases and international health. Moore and Warren formed a collaboration with Yi-Hsuan Su, one of Swami’s graduate students in electrical engineering. Su was looking at the effect of probiotics on C. difficile in culture, using the characteristic electrical polarization of C. diff to rapidly measure associated changes to the bacteria.

This collaboration piqued Moore’s interest in microfluidics and electrophysical techniques. “I could envision a lot of applications in this emerging field,” Moore said. “We had specific tools that could be used to measure changes to C. difficile rapidly as well as mouse models where we could control the damage to the microbiome through antibiotic exposure. It just made sense to combine the two techniques to develop a screening method to inform treatment decisions.”

While in Warren’s lab, Moore learned to apply the mouse model of C. difficile infection in testing the effects of diet, antibiotics and treatment in the microbiota, thereby influencing the outcome of infection. This background enabled Moore to apply electrophysiological assays in in vitro and in vivo models relevant to human disease, Warren explained. She credits Moore for effectively bridging these two distinct fields.

Moore enrolled in the electrical engineering program in the summer of 2015, joining Swami’s lab. Colleagues who originally developed electrical aspects of the cell phenotyping method, including Carlos Honrado, a postdoctoral research associate and Armita Salahi, a Ph.D. student, assisted in the effort.

“John is a transformational student,” Swami said. “He took a biophysical cell analysis tool developed within my lab, to realize its clinical application for microbiological analysis within highly complex samples.”

Moving from mouse models to a clinical setting is the next step, to see how the screening method can be adapted for predicting a patient’s susceptibility to C. diff infection.

Reducing the likelihood of recurrence is a related aim of the Moore’s research. MedLine Plus reports that about one in five people who have had C. diff will get it again. Moore collaborated with researchers in electrical and computer engineering, biomedical engineering and UVA’s School of Medicine on a method to aid treatment of recurrent C. diff infections. Their rapid screening method assesses how well probiotic combinations may restore the gut’s microbiome.

The paper, “Rapid in Vitro Assessment of Clostridioides difficile Inhibition by Probiotics Using Dielectrophoresis to Quantify Cell Structure Alterations,” was published in the April 2020 issue of the American Chemical Society’s Journal of Infectious Diseases.