Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome
| Autor: | Wen-Bing Jin, Ting-Ting Li, Da Huo, Sophia Qu, Xin V. Li, Mohammad Arifuzzaman, Svetlana F. Lima, Hui-Qing Shi, Aolin Wang, Gregory G. Putzel, Randy S. Longman, David Artis, Chun-Jun Guo |
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| Rok vydání: | 2022 |
| Předmět: |
Clostridium
Inflammation Male Mice Knockout Transcription Genetic Dextran Sulfate Gene Transfer Techniques Drug Resistance Microbial Gene Expression Regulation Bacterial Colitis General Biochemistry Genetics and Molecular Biology Gastrointestinal Microbiome Bile Acids and Salts Intestines Mice Inbred C57BL Mutagenesis Insertional Genes Bacterial RNA Ribosomal 16S Mutation Metabolome Animals Germ-Free Life Female Metagenomics CRISPR-Cas Systems |
| Zdroj: | Cell. 185:547-562.e22 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2021.12.035 |
| Popis: | Hundreds of microbiota genes are associated with host biology/disease. Unraveling the causal contribution of a microbiota gene to host biology remains difficult because many are encoded by nonmodel gut commensals and not genetically targetable. A general approach to identify their gene transfer methodology and build their gene manipulation tools would enable mechanistic dissections of their impact on host physiology. We developed a pipeline that identifies the gene transfer methods for multiple nonmodel microbes spanning five phyla, and we demonstrated the utility of their genetic tools by modulating microbiome-derived short-chain fatty acids and bile acids in vitro and in the host. In a proof-of-principle study, by deleting a commensal gene for bile acid synthesis in a complex microbiome, we discovered an intriguing role of this gene in regulating colon inflammation. This technology will enable genetically engineering the nonmodel gut microbiome and facilitate mechanistic dissection of microbiota-host interactions. |
| Databáze: | OpenAIRE |
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