Engineering the human gut commensal Bacteroides thetaiotaomicron with synthetic biology

Yong Lai; Naoki Hayashi; Timothy K Lu

doi:10.1016/j.cbpa.2022.102178

Engineering the human gut commensal Bacteroides thetaiotaomicron with synthetic biology

Curr Opin Chem Biol. 2022 Oct:70:102178. doi: 10.1016/j.cbpa.2022.102178. Epub 2022 Jun 24.

Authors

Yong Lai¹, Naoki Hayashi², Timothy K Lu³

Affiliations

¹ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
² JSR-Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp., 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
³ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA; Senti Biosciences, 2 Corporate Drive South San Francisco, CA 94080, USA. Electronic address: tim@lugroup.org.

PMID: 35759819
DOI: 10.1016/j.cbpa.2022.102178

Abstract

The role of the microbiome in health and disease is attracting the attention of researchers seeking to engineer microorganisms for diagnostic and therapeutic applications. Recent progress in synthetic biology may enable the dissection of host-microbiota interactions. Sophisticated genetic circuits that can sense, compute, memorize, and respond to signals have been developed for the stable commensal bacterium Bacteroides thetaiotaomicron, dominant in the human gut. In this review, we highlight recent advances in expanding the genetic toolkit for B. thetaiotaomicron and foresee several applications of this species for microbiome engineering. We provide our perspective on the challenges and future opportunities for the engineering of human gut-associated bacteria as living therapeutic agents.

Keywords: Bacteroides; Genetic circuits; Human gut commensal bacteria; Living medicines; Microbiota; Synthetic biology.

Publication types

Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Bacteroides thetaiotaomicron* / genetics
Humans
Microbiota*
Symbiosis
Synthetic Biology

Grants and funding

U01 CA250554/CA/NCI NIH HHS/United States