Imaging the microbiome
Normally samples of bacteria must be removed from their microbiome environment for analysis, which can lead to changes in their metabolic activity and other behaviors, hindering our ability to accurately study the gut or urogenital microbiome.
“This could be avoided if we are able to observe the bacteria in the body using Magnetic Resonance Imaging (MRI),” says Sarah Donnelly, MSc student at Lawson Health Research Institute and the Department of Microbiology and Immunology and collaborative Molecular Imaging program at Western University’s Schulich School of Medicine & Dentistry.
She is investigating the possibility of using magnetically-labelled bacteria with MRI to more directly study microbial interactions in urological and other conditions.
“The hope is that in the future we can use imaging technologies to visualize aspects of the microbiome in its healthy state compared to diseased states to see the early signs of disease and take preventative measures or allow for early intervention,” she says.
Donnelly has received a Lawson Internal Research Fund (IRF) Studentship to conduct the study, which will be supervised by Dr. Jeremy Burton, scientist in Lawson’s Human Microbiome and Probiotics research program at St. Joseph’s Health Care London (St. Joseph’s) and appointed to the Departments of Surgery and Microbiology & Immunology at Schulich Medicine & Dentistry; and Dr. Donna Goldhawk, scientist in Lawson’s Imaging research program at St. Joseph’s and assistant professor in the Department of Medical Biophysics at Schulich Medicine & Dentistry.
Escherichia coli (E. coli) are a common bacterium found in the human gut microbiome and frequently cause non-intestinal conditions like urinary tract infections. The researchers will program E. coli to express an iron uptake gene, magA. This gene is taken from another type of bacteria called magnetotactic because of their response to Earth’s magnetic field. The researchers will study whether the increase in iron uptake caused by magA expression will allow MRI to detect the magnetic signal more clearly than it would in images of untransformed E.coli. This would make it possible to see the bacteria’s behavior in living subjects without removing the bacteria cells from the microbiome environment.
They will then use this technique to study how magA labelled bacteria affect biofilm on medical devices. A biofilm is a structure produced when certain bacteria adhere to a surface and then stick together.
They will also analyze how lithotripsy affects the bacteria’s spatial distribution and interactions in three-dimensional models of kidney stones. Lithotripsy uses shockwaves to break up kidney stones into smaller pieces that are able to pass naturally out of the body. However, these shockwaves not only affect kidney stones. The waves are sent throughout the tissue, and the bacteria living on these tissues may also be affected.
“While lithotripsy is effective in treating kidney stones, we don’t know the side effects of lithotripsy on the microbiome. The shockwaves could disturb the bacteria, potentially leading to diseases caused by an imbalance between helpful and harmful bacteria,” says Donnelly.
These laboratory models will allow the researchers to perform studies in vivo (in animal models) in the future.
“Health research is very important for the development of new technologies and treatments but it is often difficult to secure funding. The IRF program allows students to pursue research that would not otherwise be possible,” explains Donnelly.
The IRF is designed to provide Lawson scientists and students the opportunity to obtain start-up funds for new projects with the potential to obtain larger funding, be published in a high-impact journal, or provide a clinical benefit to patients. Funding is provided by the clinical departments of London Health Sciences Centre and St. Joseph’s Health Care London, as well as the hospital foundations (London Health Sciences Foundation and St. Joseph’s Health Care Foundation).