Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut...

Hydrogen sulfide (H₂S) 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 H₂S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer Escherichia coli to titrate H₂S 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 H₂S 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 H₂S across a 16-fold range and induce changes in host gene expression and metabolism in an H₂S-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.