Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system
Justin A. Hayes, Anna W. Lunger, Aayushi S. Sharma, Matthew T. Fernez, Rebecca L. Carrier, Abigail N. Koppes, Ryan A. Koppes, Benjamin M. Woolston
Abstract
Hydrogen sulfide (H 2 S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H 2 S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer Escherichia coli to titrate H 2 S across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip is engineered to maintain H 2 S gas tension and enables visualization of co-culture in real time with confocal microscopy. Engineered strains colonize the chip and are metabolically active for 2 days, during which they produce H 2 S across a 16-fold range and induce changes in host gene expression and metabolism in an H 2 S-concentration-dependent manner. These results validate a platform for studying the mechanisms underlying microbe-host interactions by enabling experiments that are infeasible with current animal and in vitro models.