Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.

Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.
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DOI:
10.1016/j.cell.2021.12.035
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发表时间:
2022-02-03
期刊:
影响因子:
64.5
通讯作者:
Guo CJ
Guo CJ
中科院分区:
生物学1区
文献类型:
--
作者:
Jin WB;Li TT;Huo D;Qu S;Li XV;Arifuzzaman M;Lima SF;Shi HQ;Wang A;Putzel GG;Longman RS;Artis D;Guo CJ

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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 non-model 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 non-model microbes spanning 5 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 discover an intriguing role of this gene in regulating colon inflammation. This technology will enable genetically engineering the non-model gut microbiome and facilitate mechanistic dissection of microbiota-host interactions. A pipeline for the genetic manipulation of non-model gut microbes enables single- gene, functional interrogation of bacteria in a complex microbial system
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