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

• Published in: Cell reports (Cambridge) 2023-12, Vol.42 (12), p.113481-113481, Article 113481
• Main Authors: Hayes, Justin A., Lunger, Anna W., Sharma, Aayushi S., Fernez, Matthew T., Carrier, Rebecca L., Koppes, Abigail N., Koppes, Ryan, Woolston, Benjamin M.
• Format: Article
• Language: English
• Subjects: bioengineering; CP: Microbiology; gut metabolome; gut microbiome; gut microphysiological system; gut on a chip; host-microbe interactions; hydrogen sulfide; inflammatory bowel disease; metabolic engineering; synthetic biology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113481

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. [Display omitted] •Gut microphysiological system (GMPS) maintains gas tension of volatile gasotransmitter H2S•Engineered E. coli titrates H2S, is metabolically active, and colonizes GMPS for two days•GMPS enables visualization of host-microbe interactions•Microbial H2S induces dose-dependent effects on Caco-2 gene expression and metabolism Hayes et al. demonstrate a platform to interrogate the causal role of gaseous microbial metabolites in a low-gas-permeable, humanized gut microphysiological system, enabling high-resolution analysis of host-microbe interactions. E. coli was engineered to titrate hydrogen sulfide levels, which induced dose-dependent effects on host gene expression and metabolism.