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Engineering the gut microbiome

Nature Reviews Bioengineering volume 1, pages 665–679 (2023)Cite this article

Subjects

Abstract

The role of the gut microbiome in human health and disease is being increasingly recognized. Gut microbes (including bacteria, fungi and viruses) can be genetically modified to diagnose (as biosensors) and treat (detoxification, controlled biosynthesis and precision targeting) the dysbiosis of the microbiome, which has been linked to several cancers and metabolic, autoimmune and infectious diseases. However, conventional manipulation of single microbial strains is often insufficient, and engineering a mutually supportive and collaborative network of gut microbes — ‘a keystone consortium’ — could be more effective. In this Review, we summarize gut microbiome engineering strategies against selected diseases and critically discuss their translational potential. We focus mainly on genetic engineering approaches, but we also discuss complementary strategies such as encapsulation, coupling with electronic devices, orthogonal diet engineering and faecal microbiota transplantation.

Key points

  • The human gastrointestinal (GI) tract contains thousands of microbial species, including bacteria, fungi and viruses, the dysbiosis of which has been linked to the pathogenesis of many diseases.

  • The microbiome can be engineered to treat various pathologies including cancer, metabolic and autoimmune diseases.

  • ‘Holistic’ modulation of the gut microbiome through orthogonal approaches and/or engineering mutually supportive and collaborative networks of gut microbes is an emerging and promising alternative to engineering single microbes.

  • Proper biocontainment and precision targeting are among the main challenges to be overcome for the clinical translation of gut microbiome engineering strategies.

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Fig. 1: Milestones of microbial engineering.
Fig. 2: Strategies for the holistic modulation of gut microorganisms.
Fig. 3: Translational applications of engineered microbes as disease therapeutics.

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Acknowledgements

T.Z. discloses support for publication of this work from the National Natural Science Foundation of China (NSFC grant numbers 82172323 and 32100134), the Municipal Key Research and Development Program of Guangzhou (grant number 202206010014). We acknowledge intellectual support from the Key Laboratory of Human Microbiome and Chronic diseases (Sun Yat-sen University), Ministry of Education, China.

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Author notes

  1. Benjamin M. Scott

    Present address: Global Institute for Food Security, University of Saskatchewan, Saskatoon, Canada

  2. These authors contributed equally: Xiaowu Bai, Ziyu Huang.

Authors and Affiliations

  1. Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Xiaowu Bai, Ziyu Huang & Tao Zuo

  2. Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China

    Xiaowu Bai, Ziyu Huang & Tao Zuo

  3. Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Ziyu Huang & Tao Zuo

  4. Department of Biological Systems Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA

    Anna M. Duraj-Thatte

  5. Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    Matthias P. Ebert & Elke Burgermeister

  6. DKFZ-Hector Cancer Institute, Mannheim, Germany

    Matthias P. Ebert

  7. Mannheim Cancer Centre (MCC), University Medical Centre, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Matthias P. Ebert

  8. College of Science and Engineering, Jinan University, Guangzhou, China

    Fen Zhang

  9. Department of Pathogen Biology, Faculty of Medicine, Shenzhen University, Shenzhen, China

    Xue Liu

  10. Centre for Applied Synthetic Biology, Concordia University, Montréal, QC, Canada

    Benjamin M. Scott

  11. Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumour, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China

    Guoxin Li

  12. Laboratory Animals Centre, Sun Yat-sen University, Guangzhou, China

    Tao Zuo

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Contributions

T.Z. conceived the manuscript. X.B., Z.H. and T.Z. wrote the manuscript. B.M.S., A.M.D.-T., M.P.E, F.Z., X.L. and E.B. provided substantial intellectual contributions and revised the manuscript. T.Z. and G.L. supervised this study and the drafting of this manuscript.

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Correspondence to Guoxin Li or Tao Zuo.

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Bai, X., Huang, Z., Duraj-Thatte, A.M. et al. Engineering the gut microbiome. Nat Rev Bioeng 1, 665–679 (2023). https://doi.org/10.1038/s44222-023-00072-2

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