Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.
Animals
Bile Acids and Salts
/ metabolism
CRISPR-Cas Systems
/ genetics
Clostridium
/ genetics
Colitis
/ chemically induced
Dextran Sulfate
Drug Resistance, Microbial
/ genetics
Female
Gastrointestinal Microbiome
/ genetics
Gene Expression Regulation, Bacterial
Gene Transfer Techniques
Genes, Bacterial
Germ-Free Life
Inflammation
/ pathology
Intestines
/ pathology
Male
Metabolome
/ genetics
Metagenomics
Mice, Inbred C57BL
Mice, Knockout
Mutagenesis, Insertional
/ genetics
Mutation
/ genetics
RNA, Ribosomal, 16S
/ genetics
Transcription, Genetic
Firmicutes/Clostridia
bile acid metabolism
colitis
complex gut microbiome
genetic manipulation tools
host-microbe interactions
nonmodel gut microbes
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
03 02 2022
03 02 2022
Historique:
received:
03
08
2020
revised:
01
11
2021
accepted:
21
12
2021
pubmed:
21
1
2022
medline:
25
2
2022
entrez:
20
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35051369
pii: S0092-8674(21)01541-5
doi: 10.1016/j.cell.2021.12.035
pmc: PMC8919858
mid: NIHMS1772416
pii:
doi:
Substances chimiques
Bile Acids and Salts
0
RNA, Ribosomal, 16S
0
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
547-562.e22Subventions
Organisme : NIAID NIH HHS
ID : R21 AI142213
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095466
Pays : United States
Organisme : NICHD NIH HHS
ID : DP2 HD101401
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126871
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI151599
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128257
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI095608
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114252
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.A. has contributed to scientific advisory boards at Genentech, Pfizer, Takeda, FARE, and the KRF. The other authors declare no competing interests. A provisional patent application has been filed by the Weill Cornell Center for Technology Licensing based on this work.
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