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Decoding the microbiome: advances in genetic manipulation for gut bacteria.

Ziying Chen1, Wenbing Jin2, Alex Hoover3

  • 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200031, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200031, China; The Center for Microbes, Development and Health (CMDH), CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

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Summary

Developing genetic manipulation (GM) tools for gut bacteria is crucial for understanding host-microbiome interactions. These tools, like CRISPR-Cas, enable microbiome engineering for treating diseases such as cancer and metabolic disorders.

Keywords:
CRISPR-Casgenetic manipulation toolsgut microbiomehost–microbe interactionstransposon

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Area of Science:

  • Microbiology
  • Genetics
  • Gastroenterology

Background:

  • Gut microbiota composition is linked to health and disease, but causal mechanisms of gene-host interactions are unclear.
  • Limited genetic manipulation (GM) tools for gut bacteria hinder research into these mechanisms.

Purpose of the Study:

  • To review advances and challenges in developing GM tools for gut bacteria.
  • To highlight the potential of GM tools for understanding host-microbiome associations and engineering the microbiome for clinical applications.

Main Methods:

  • Review of current genetic manipulation technologies, including CRISPR-Cas and transposase-based systems.
  • Discussion of GM tool application in both model and non-model gut bacteria.

Main Results:

  • GM tools are advancing, offering new ways to study gut bacteria.
  • Successful application of GM tools can elucidate molecular mechanisms of host-microbiome interactions.
  • Engineered microbiomes hold promise for treating cancer and metabolic disorders.

Conclusions:

  • Overcoming barriers in gut microbiome manipulation is key to advancing molecular understanding.
  • Developing generalized GM pipelines is essential for accelerating the application of these tools in non-model gut bacteria.
  • Further development of GM tools will drive both basic research and clinical translation for microbiome-based therapies.