Metformin-induced reductions in tumor growth involves modulation of the gut microbiome.
Mol Metab
; 61: 101498, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35452877
ABSTRACT
BACKGROUND/PURPOSE:
Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce colorectal cancer but the mechanisms mediating this effect remain unclear. In mice and humans, a high-fat diet (HFD), obesity and metformin are known to alter the gut microbiome but whether this is important for influencing tumor growth is not known.METHODS:
Mice with syngeneic MC38 colon adenocarcinomas were treated with metformin or feces obtained from control or metformin treated mice.RESULTS:
We find that compared to chow-fed controls, tumor growth is increased when mice are fed a HFD and that this acceleration of tumor growth can be partially recapitulated through transfer of the fecal microbiome or in vitro treatment of cells with fecal filtrates from HFD-fed animals. Treatment of HFD-fed mice with orally ingested, but not intraperitoneally injected, metformin suppresses tumor growth and increases the expression of short-chain fatty acid (SCFA)-producing microbes Alistipes, Lachnospiraceae and Ruminococcaceae. The transfer of the gut microbiome from mice treated orally with metformin to drug naïve, conventionalized HFD-fed mice increases circulating propionate and butyrate, reduces tumor proliferation, and suppresses the expression of sterol response element binding protein (SREBP) gene targets in the tumor.CONCLUSION:
These data indicate that in obese mice fed a HFD, metformin reduces tumor burden through changes in the gut microbiome.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Diabetes Mellitus Tipo 2
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Microbioma Gastrointestinal
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Metformina
Limite:
Animals
Idioma:
En
Revista:
Mol Metab
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá