Centre for Blood Research Seminar – “Leveraging the gut environment for functional biosensor probiotics”

From the lab of: Dr. Carolina Tropini, Department of Microbiology and Immunology, UBC.

Presented by: Carolina Tropini and Alice Hong.

The human gut is a complex, dynamic ecosystem characterized by a diverse community of microbes that play critical roles in health and disease. Physical factors such as osmolality, pH, and oxygenation profoundly influence microbial growth, community structure, and function. Yet, how such physical factors shape the gut microbiome, particularly under disease-associated conditions, remains underexplored. Given the gut’s natural mosaic of localized niches, where distinct physical environments shape unique microbial communities, it is essential to understand how these factors influence microbiota structure and function.

Our work aims to harness the gut’s physical landscape as a blueprint for engineering next-generation biosensor probiotics. By integrating insights from physical microbiology with synthetic biology, we are developing genetically engineered probiotics capable of sensing and reporting on critical gut parameters. Our approach uses prominent and genetically tractable gut commensal bacteria to build biosensors that detect environmental shifts. In proof-of-concept studies, we engineered biosensors responsive to malabsorption conditions, demonstrating their ability to detect physiologically relevant shifts in environmental conditions through graded fluorescent outputs in both in vitro and in vivo models. These biosensors enabled near real-time, non-invasive monitoring of single-cell responses in a murine model of malabsorption, revealing the potential of gut-resident bacteria as diagnostic platforms for diverse gastrointestinal disorders.

By integrating biophysical understanding with cutting-edge genetic tools, this work highlights the potential of engineered gut probiotics to transform our ability to monitor and manage gut health, bridging the gap between microbiome research and precision diagnostics.