A Synthetic Inter-Species Information Transfer System Functions in the Mammalian Gut

The gut microbiome has many crucial roles in establishing and maintaining the health of the host. These roles depend on the composition of the microbiome as well as the interactions among the microbes and with the host. The gut microbiome can be reshaped through various measures, such as dietary changes, antibiotic treatments, and fecal transplants. However, these approaches result in wholesale changes with limited levels of control and definition. Precise engineering of gut microbes poses an opportunity to overcome these limitations and expand the scope of control over the gut microbiome. Here, we present how we engineered bacterial cells to communicate and share information to one another to form hierarchical responses to a master signal in the complex environment of the mammalian gut. Specifically, we have taken two genetic circuits – one for cellular sensing and signaling and the other for memory – and integrated them into a robust information transfer system that can function to report on cell interactions in the mammalian gut. This system provides a basis for further understanding of inter-bacterial interactions in an otherwise hard-to-study environment as well as a basis for construction of a programmable gut consortia.