Metformin-induced reductions in tumor growth involves modulation of the gut microbiome

• DOI: 10.1016/j.molmet.2022.101498
• Publication Date: 2022-04-20T21:20:22Z
• Authors: Lindsay A. Broadf...; Amna Saigal; Jake C. Szamosi; Joanne A. Hammill; Ksenia Bezverbnaya; Dongdong Wang; Jaya Gautam; Evangelia E. Tsak...; Fiorella Di Pastena; Jamie McNicol; Jianhan Wu; Saad Syed; James S.V. Lally; Amogelang R. Raph...; Marie-Jose Blouin; Michael Pollak; Andrea Sacconi; Giovanni Blandino; Andrew G. McArthur; Jonathan D. Scher...; Michael G. Surette; Stephen M. Collins; Jonathan L. Bramson; Paola Muti; Theodoros Tsakiridis; Gregory R. Steinberg
• Keywords: Lachnospiraceae

Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce cancer but mechanisms mediating this effect remain unclear. In mice humans, a high-fat diet (HFD), metformin are known to alter gut microbiome whether is important for influencing tumor growth not known. Mice with syngeneic MC38 colon adenocarcinomas were treated or feces obtained from control mice. We find that compared chow-fed controls, increased when fed HFD acceleration can be partially recapitulated through transfer fecal in vitro treatment cells filtrates HFD-fed animals. Treatment orally ingested, intraperitoneally injected, suppresses increases expression short-chain fatty acid (SCFA)-producing microbes Alistipes, Lachnospiraceae Ruminococcaceae. The drug naïve, conventionalized circulating propionate butyrate, reduces proliferation, sterol response element binding protein (SREBP) gene targets tumor. These data indicate obese HFD, burden changes microbiome.