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bioRxiv · 10.1101/2023.05.16.538950

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

Hayes, J. A.·Lunger, A. W.·Sharma, A. S.·Fernez, M. T.·Koppes, R. A.·Koppes, A. N.·Woolston, B. M.
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Abstract

Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non-representative model systems in previous work. Here, we engineered E. coli to titrate H2S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H2S gas tension and enable visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a novel platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal and in vitro models.

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Hayes, J. A., Lunger, A. W., Sharma, A. S., Fernez, M. T., Koppes, R. A., Koppes, A. N., Woolston, B. M.. 2023-05-16. Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system. https://doi.org/10.1101/2023.05.16.538950

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