Estradiol modulates gut microbiota in female ob/ob mice fed a high fat diet

Estrogens protect against diet-induced obesity in women and female rodents. In support of these anorectic effects, lack of estrogens in postmenopausal women is associated with weight gain, increasing their risk for cardiovascular diseases and cancer. Estrogens act with leptin, a satiety hormone encoded by the ob gene, to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. In addition to estrogens and leptin, the gut microbiome (gut microbes and their metabolites), is critical in regulating energy metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) control mice fed a high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes compared to vehicle counterparts. Moreover, both obesity (ob/ob mice) and E2 reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared to vehicle mice. Regarding taxa, E2 treatment was associated with higher abundances of the family S24-7. Leptin was associated with higher abundances of Coriobacteriaceae, Clostridium and Lactobacillus. E2 and leptin had overlapping effects on relative abundances of some taxa, suggesting that interaction of these hormones is important in gut microbial homeostasis. Taken together, these findings suggest that E2 and leptin profoundly alter the gut microbiota of HFD-fed female mice. Understanding the function of E2 and leptin in regulating gut microbiota will allow the development of therapies targeting the gut microbiome for hormone-dependent metabolic disorders in women.