By Sarah Kasleder for SHRF
The connection between gut health and mental wellness might be the secret to transforming how we treat Crohn’s disease.
Dr. Amanda Hall and her team are leading this charge by researching the creation of a novel organoid model to explore the gut-brain axis in inflammatory bowel disease. They have been recently awarded the Saskatchewan Health Research Foundation (SHRF) Excellence Award for the top-ranked 2024-25 Establishment Grant. This award, given by SHRF, recognizes outstanding researchers making significant contributions to health science. Dr. Hall’s award highlights the impact of her interdisciplinary research in tackling the complex challenges of Crohn's disease—particularly its effects on the gut and the brain.
Understanding Crohn’s Disease
Crohn’s disease is a type of inflammatory bowel disease (IBD) that causes chronic inflammation of the digestive tract. Crohn’s can impact any part of the digestive system, from the mouth to the end of the intestines. This inflammation can lead to various symptoms, including abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. Crohn’s disease is a lifelong condition that can cause significant discomfort and complications, and while treatments are available to manage symptoms, there is currently no cure. The exact cause of Crohn’s is still unknown, but it is believed to result from a combination of genetic, environmental, and immune system factors. The disease not only affects the digestive system but is also associated with other health issues, such as mental health disorders, highlighting the need for thorough and well-rounded approaches to treatment.
The Birth of a Groundbreaking Project
Dr. Hall’s research is grounded in the hypothesis that the inflammation observed in Crohn's disease is not confined to the gastrointestinal tract but also manifests in the brain, potentially contributing to mental health issues among Crohn's patients.
This innovative project was born from a fortunate encounter between Dr. Hall and Dr. Tyler Wenzel in their shared Health Sciences building. "We were both working on organoids—my team on intestines and his on brains. It was clear that we could do something unique by combining our efforts," Dr. Hall shared. This meeting sparked a collaboration that could revolutionize our understanding and treatment of Crohn’s disease.
The Research Project: A Collaborative Effort
Dr. Hall's research is a collaborative effort involving three departments: her lab, which focuses on developing intestinal organoids; Dr. Tyler Wenzel’s expertise in brain organoids; and Dr. Sharyle Fowler from the Department of Gastroenterology, which provides critical clinical context. Together, they are developing a model investigating the inflammatory crosstalk between the brain and gut in Crohn's patients—a connection that has long been suspected but is not yet fully understood.
The brain and gut communicate through a complex network known as the gut-brain axis. This communication occurs via the vagus nerve, the bloodstream, and immune system signalling. In Crohn’s disease, inflammation in the gut can trigger a cascade of chemical signals that travel to the brain, potentially leading to neurological symptoms like anxiety and depression. Conversely, stress and mental health issues can worsen gut inflammation, creating a vicious cycle of symptoms.
"As we delve deeper into the gut-brain axis, it becomes clear that the inflammation in Crohn’s disease is not just limited to the gut," Dr. Hall noted. "The same inflammatory signals that wreak havoc in the digestive tract are likely causing changes in the brain as well, which could explain why so many Crohn’s patients experience mental health challenges."
The Goal: A Holistic Approach to Treatment
The primary aim of Dr. Hall’s project is to build a model that can accurately replicate Crohn's disease's intestinal and neurological impacts. To achieve this, her team is developing patient-specific organoid models—miniature, lab-grown versions of the gut and brain—created from stem cells derived from Crohn’s patients. These organoids will mimic the unique inflammatory environment of Crohn's disease, allowing researchers to observe how inflammation in the gut can trigger changes in the brain and vice versa.
"By using stem cells from actual Crohn's patients, we're able to create models that closely mirror the specific ways the disease manifests in different individuals," Dr. Hall explained. "This allows us to see the inflammatory processes at work and how they might contribute to gut and brain symptoms."
These models will enable researchers to study the movement of inflammatory signals between the gut and brain and how they contribute to gastrointestinal and neurological symptoms in Crohn’s patients. "Our goal is to create a model that not only replicates the intestinal damage caused by Crohn's but also the neurological changes accompanying it," Dr. Hall said.
The insights gained from this research could lead to new treatments that address the physical and mental health aspects of Crohn’s disease, offering a more holistic approach to patient care. "Right now, treatments for Crohn's and its associated mental health issues are often handled separately, which can be ineffective or even counterproductive," said Dr. Hall. "Our long-term vision is to create personalized treatment plans using these organoid models to test and predict the efficacy of different therapies before applying them in real-life scenarios."
The Future: Personalized Medicine and Beyond
The implications of Dr. Hall’s research are vast. If successful, the model could lead to the development of personalized treatments for Crohn’s disease tailored to the specific needs of individual patients. This would be particularly beneficial given the varied nature of Crohn’s and the differences in how patients respond to treatment.
Looking ahead, Dr. Hall is excited about the potential of this research. "This project could be the foundation for an entire research program," she said. "We know that there are at least 3,000 people with Crohn’s in Saskatchewan alone, many of whom also struggle with mental health issues. This research can potentially make a real difference in their lives."
Final Thoughts: The Power of Collaboration
As Dr. Hall reflects on her work, she emphasizes the importance of collaboration in achieving these breakthroughs. "We’re better together," she noted. "This project is a perfect example of how bringing together different areas of expertise can lead to something truly innovative and impactful."
Dr. Hall's work is paving the way for a brighter future for those with Crohn's disease, offering the possibility of more effective, holistic treatments. With continued research and collaboration, the day Crohn's patients receive genuinely personalized care may be closer than we think.