Toward Microbiome Engineering: Expanding the Repertoire of Genetically Tractable Members of the Human Gut Microbiome.

Genetic manipulation is necessary to interrogate the functions of microbes in their environments, such as the human gut microbiome. Yet, the vast majority of human gut microbiome species are not genetically tractable. Here, we review the hurdles to seizing genetic control of more species. We address the barriers preventing the application of genetic techniques to gut microbes and report on genetic systems currently under development. While methods aimed at genetically transforming many species simultaneously in situ show promise, they are unable to overcome many of the same challenges that exist for individual microbes. Unless a major conceptual breakthrough emerges, the genetic tractability of the microbiome will remain an arduous task. Increasing the list of genetically tractable organisms from the human gut remains one of the highest priorities for microbiome research and will provide the foundation for microbiome engineering.