Drs. Carolina Tropini (left) and Annie Ciernia (right) are recipients of the UBC Faculty of Medicine 2021/2022 Precision Health Catalyst Grant award for their project titled “Metabolite Control of Microbiome-Microglia Communication in Pediatric Inflammatory Bowel Disease (IBD)”
Read a summary of the project here.
Can you tell us how the gut microbiome is related to precision health?
CT: Human health is intimately connected with the tens of trillions of bacteria, fungi and viruses that live symbiotically in and on our bodies. Our microbiota is a remarkable consortium of microbes, unique to each person, and is constantly evolving and adapting. Gut microbes produce compounds that are directly absorbed into our blood, both nourishing us and affecting human functions as diverse as digestion, immunity, and neurodegeneration. The gut microbiota is also malleable, making this ecosystem an enticing target for precision medicine.
How are you collaborating on your current research project?
AC: We are working on understanding the link between the gut microbiome and the developing brain. My lab specifically focuses on microglia, the innate immune cells of the brain. Microglia are heavily influenced during early brain development by signals from the gut microbiome. Disorders that cause inflammation of the gut during childhood and adolescence may disrupt these signals, negatively impacting how microglia develop and function. Microglia help regulate a diverse set of neurodevelopmental processes and disruption of these functions may negatively impact brain development and increase later life disease risk.
CT: We are investigating how a disrupted gut environment in diseases such as inflammatory bowel disease (IBD) affect the microbiota and host at a multi-scale level. Specifically, in this exciting collaboration with the Ciernia lab, we are investigating how individual IBD patient microbiota affect host health, brain, and sexual development in animal models. We are working on developing precision therapies to restore a normal microbiota and reduce the impact of IBD.
What results have you seen so far?
AC: In a mouse model of Inflammatory Bowel Disease (IBD), we induce gut inflammation artificially in young mice, simulating childhood onset IBD in humans. We can then assess impacts on the developing brain microglia and critical developmental milestones in behaviour development. So far, we have identified several key metabolites released by the gut microbiome that specifically signal to brain microglia. These metabolites are decreased in the young IBD mice, which also show abnormal social and cognitive development. Our future work will attempt to reverse these deficits in brain and behaviour by supplementing the young IBD mice with either the metabolites or missing microbes. The long-term goal will be to identify changes in individual patient’s microbiomes and metabolomes to allow for precision medicine based microbiota therapies.
What role does precision health play in childhood health research?
CT: In our research we are learning that the specific make-up of the microbiota affects what compounds (metabolites) are found in blood, which can influence the development of every organ during childhood and beyond. The composition of the blood metabolites in every child is different, and our bodies are generally very robust to small changes due to diet, sickness, or other disturbances. However, depending on the genetic make-up of an individual, their general diet and microbiota, there may be metabolites that are missing or unbalanced. This can worsen health outcomes, which we want to target with precision medicine. For example, we are finding that in some IBD microbiota there are missing bacteria that normally produce anti-inflammatory compounds. By restoring the missing microbes, we are aiming to decrease inflammation not only in the gut, but also in other organs such as the brain.
AC: Childhood is such a critical time for brain development and disruptions to development have life-long consequences for health and disease risk. By employing precision medicine techniques early in life, we could restore the normal developmental trajectory and effectively eliminate long-term complications.
From your perspective, what do you think is exciting about the future direction of precision health?
AC: One of the most important aspects is the focus on moving from away from treating disease to promoting health. By moving away from healthcare based on averages and moving towards integration of multiple metrics across time for a single individual, I think precision medicine will allow each of us to take better charge of our own health. By making this data accessible to people, we will all be able to make better choices that will ultimately lead to higher quality of life and lower disease burden.
CT: Interdisciplinary collaborations are paving a new way of doing precision medicine, one that has a more holistic approach and wide-ranging impacts. For example, in our collaboration with the Ciernia lab we are learning about the widespread effects of gut inflammation, which can affect cognition and behaviour, as well as overall development. By learning about the multi-faceted aspects of a disease we can come up with therapies that are both more specific to the individual while also targeting a broader set of disease effects.
About Dr. Carolina Tropini
Dr. Carolina Tropini is an Assistant Professor at the University of British Columbia in the Department of Microbiology and Immunology and the School of Biomedical Engineering. She is a Paul Allen Distinguished Investigator and in 2020 she was the first Canadian to be awarded the Johnson & Johnson Women in STEM2D Scholar in the field of Engineering. She is a CIFAR Fellow in the Human & the Microbiome Program and a Michael Smith Foundation for Health Research Scholar. In 2019, she was nominated as a CIFAR Azrieli Global Scholar.
The Tropini lab is investigating how a disrupted physical environment due to altered nutrition or concurrent with intestinal diseases affects the microbiota and host at a multi-scale level. They are a cross-disciplinary group that incorporates techniques from microbiology, bioengineering and biophysics to create highly parallel assays and study how bacteria and microbial communities function, with the goal of translating the knowledge gained to improve human health.
About Dr. Annie Ciernia
Dr. Ciernia is an Assistant Professor in Biochemistry and Molecular Biology and the Tier 2 Canada Research Chair for Understanding Gene Expression in the Brain. Her lab is focused on studying how gene expression is regulated in the brain during development and disease. Dr. Ciernia’s lab combines experimental and computational approaches to understand how different brain cell types regulate gene expression across our lifespan. Her lab specifically focuses on mechanisms of epigenetic regulation in rodent models of neuro-immune interactions. Her group tests novel hypotheses linking genetic and environmental risk factors to altered patterns of gene expression, epigenomic regulatory pathways, cellular function and animal behaviour. Findings from Dr. Ciernia’s research increase our understanding of the mechanisms regulating gene expression in the brain during neuroinflammation and form the basis for future development of novel immune targeted therapeutics.
