@article {Guevara-Cruze000948, author = {Martha Guevara-Cruz and Einar T Godinez-Salas and Monica Sanchez-Tapia and Gonzalo Torres-Villalobos and Edgar Pichardo-Ontiveros and Rocio Guizar-Heredia and Liliana Arteaga-Sanchez and Gerardo Gamba and Raul Mojica-Espinosa and Alejandro Schcolnik-Cabrera and Omar Granados and Adriana L{\'o}pez-Barradas and Ariana Vargas-Castillo and Ivan Torre-Villalvazo and Lilia G Noriega and Nimbe Torres and Armando R Tovar}, title = {Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects}, volume = {8}, number = {1}, elocation-id = {e000948}, year = {2020}, doi = {10.1136/bmjdrc-2019-000948}, publisher = {BMJ Specialist Journals}, abstract = {Objective Obesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity.Research design and methods 45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of >=30 and<=40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation.Results In the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5'-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of β-oxidation and ω-oxidation, acyl-carnitines and ketone bodies.Conclusions Change in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.}, URL = {https://drc.bmj.com/content/8/1/e000948}, eprint = {https://drc.bmj.com/content/8/1/e000948.full.pdf}, journal = {BMJ Open Diabetes Research and Care} }