Metformin-induced reductions in tumor growth involves modulation of the gut microbiome.
Mol Metab
; 61: 101498, 2022 07.
Article
en 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
3_ND
Problema de salud:
1_doencas_nao_transmissiveis
/
3_zoonosis
Asunto principal:
Neoplasias Colorrectales
/
Diabetes Mellitus Tipo 2
/
Microbioma Gastrointestinal
/
Metformina
Límite:
Animals
Idioma:
En
Revista:
Mol Metab
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá