Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance.
Animals
Biomarkers
Cell Line, Tumor
Cell Proliferation
/ drug effects
Colorectal Neoplasms
/ metabolism
Disease Models, Animal
Energy Metabolism
Gastrointestinal Microbiome
Glutathione
/ metabolism
Glyceraldehyde
/ analogs & derivatives
Host Microbial Interactions
Humans
Intestinal Mucosa
/ metabolism
Metabolomics
/ methods
Metagenomics
/ methods
Mice
Models, Biological
Oxidation-Reduction
/ drug effects
Oxidative Stress
Propane
/ metabolism
Signal Transduction
Xenograft Model Antitumor Assays
Lactobacillus reuteri
Microbiome
Reuterin
colorectal cancer
metabolites
protein oxidation
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
14 02 2022
14 02 2022
Historique:
received:
05
08
2021
revised:
01
11
2021
accepted:
30
11
2021
pubmed:
25
12
2021
medline:
15
3
2022
entrez:
24
12
2021
Statut:
ppublish
Résumé
Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We find that microbial metabolites from healthy mice or humans are growth-repressive, and this response is attenuated in mice and patients with CRC. Microbial profiling reveals that Lactobacillus reuteri and its metabolite, reuterin, are downregulated in mouse and human CRC. Reuterin alters redox balance, and reduces proliferation and survival in colon cancer cells. Reuterin induces selective protein oxidation and inhibits ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricts colon tumor growth, increases tumor reactive oxygen species, and decreases protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.
Identifiants
pubmed: 34951957
pii: S1535-6108(21)00613-9
doi: 10.1016/j.ccell.2021.12.001
pmc: PMC8847337
mid: NIHMS1766205
pii:
doi:
Substances chimiques
Biomarkers
0
3-hydroxypropionaldehyde
2134-29-4
Glyceraldehyde
367-47-5
Glutathione
GAN16C9B8O
Propane
T75W9911L6
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
185-200.e6Subventions
Organisme : NCI NIH HHS
ID : R01 CA148828
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095201
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA245546
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA257292
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244931
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099280
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007315
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS127371
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA264414
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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