What is the key challenge in engineering microbiomes?

The microbiome functions that we aim to engineer emerge from a myriad of unknown and dynamic cellular interactions. These functions range from driving biogeochemical cycles in the environment to enabling colonization resistance to invading pathogens in host-associated microbiomes. Depending on the application, these functions can be major contributors to a process or significant minor contributors to a process. In the latter case, even the most effective engineering of microbiomes may only moderately change a given process since other factors beyond the microbiome are the dominant drivers. Therefore, we should prioritize applications in which the microbiome is a major determinant of the target process.