PT - JOURNAL ARTICLE AU - Kalpana D Acharya AU - Xing Gao AU - Elizabeth P Bless AU - Jun Chen AU - Marc J Tetel TI - Estradiol modulates gut microbiota in female <em>ob/ob</em> mice fed a high fat diet AID - 10.1101/612283 DP - 2019 Jan 01 TA - bioRxiv PG - 612283 4099 - http://biorxiv.org/content/early/2019/04/18/612283.short 4100 - http://biorxiv.org/content/early/2019/04/18/612283.full AB - Estrogens protect against diet-induced obesity in females. For example, loss of estrogens in postmenopausal women is associated with an increased risk of weight gain. Furthermore, ovariectomized rodents on a high-fat diet (HFD) become obese, which can be prevented by estrogen treatment. Estrogens act with other hormones, including leptin, to regulate energy homeostasis in females. Leptin, a hormone encoded by the ob gene, is produced by adipocytes and acts in brain to signal satiety. 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 metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (Het; lean) control mice fed a HFD that received either 17β-Estradiol or vehicle implants. E2 attenuated weight gain in both genotypes compared to their vehicle counterparts. Moreover, both obesity (in ob/ob mice) and E2 reduced gut microbial alpha diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared to vehicle mice. At the taxa level, E2 treatment was associated with higher abundances of the S24-7 family. Leptin was associated with higher abundances of Coriobacteriaceae and the Clostridium and Lactobacillus spp. The present findings suggest that E2 and leptin profoundly alter the gut microbiota of HFD-fed female mice. Understanding the role of E2 and leptin in modulating gut microbiota will allow the development of therapeutic options targeting the gut microbiome for hormone-dependent metabolic disorders in women.