title: Microbiome therapeutics - Advances and challenges.
abstract: The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota.
authors.affiliation: MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA, USA; MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Mimee
authors.affiliation: MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA, USA; MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Citorik
authors.affiliation: MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA, USA; MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA. Electronic address: timlu@mit.edu.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lu
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D057005:Bioengineering; D006801:Humans; D064307:Microbiota; D019936:Probiotics / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents
keywords: Bacteriophage; Host-bacteria interactions; Microbial ecology; Microbiome; Synthetic biology