4.7 Review

Microbiome therapeutics - Advances and challenges

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 105, Issue -, Pages 44-54

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2016.04.032

Keywords

Microbiome; Host-bacteria interactions; Microbial ecology; Synthetic biology; Bacteriophage

Funding

  1. National Institutes of Health [DP2 OD008435, P50 GM098792, R01 EB017755]
  2. Office of Naval Research [N00014-13-1-0424]
  3. National Science Foundation [MCB-1350625]
  4. Center for Microbiome Informatics and Therapeutics
  5. Defense Threat Reduction Agency [HDTRA1-14-1-0007, HDTRA1-15-1-0050]
  6. Defense Advanced Research Projects Agency

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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. (C) 2016 Published by Elsevier B.V.

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