Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice
Kalpana D. Acharya,
Hye L. Noh,
Madeline E. Graham,
Sujin Suk,
Randall H. Friedline,
Cesiah C. Gomez,
Abigail E. R. Parakoyi,
Jun Chen,
Jason K. Kim,
Marc J. Tetel
Affiliations
Kalpana D. Acharya
Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA
Hye L. Noh
Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Madeline E. Graham
Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA
Sujin Suk
Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Randall H. Friedline
Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cesiah C. Gomez
Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA
Abigail E. R. Parakoyi
Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA
Jun Chen
Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
Jason K. Kim
Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Marc J. Tetel
Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.
