Alterations in Gut Microbiota Do Not Play a Causal Role in Diet-independent Weight Gain Caused by Ovariectomy

Abstract

Acute estrogen deficiency in women can occur due to many conditions including hyperprolactinemia, chemotherapy, GnRH agonist treatment, and removal of hormone replacement therapy. Ovariectomized (OVX) rodent models, often combined with a high-fat diet (HFD), have been used to investigate the effects of decreased estrogen production on metabolism. Since evidence suggests that gut microbes may facilitate the protective effect of estrogen on metabolic dysregulation in an OVX + HFD model, we investigated whether the gut microbiome plays a role in the diet-independent weight gain that occurs after OVX in adult female mice. 16S rRNA gene sequence analysis demonstrated that OVX was not associated with changes in overall gut bacterial biodiversity but was correlated with a shift in beta diversity. Using differential abundance analysis, we observed a difference in the relative abundance of a few bacterial taxa, such as Turicibacter, 3 to 5 weeks after OVX, which was subsequent to the weight gain that occurred 2 weeks postsurgery. A cohousing study was performed to determine whether exposure to a healthy gut microbiome was protective against the development of the metabolic phenotype associated with OVX. Unlike mouse models of obesity, HFD maternal-induced metabolic dysregulation, or polycystic ovary syndrome, cohousing OVX mice with healthy mice did not improve the metabolic phenotype of OVX mice. Altogether, these results indicate that changes in the gut microbiome are unlikely to play a causal role in diet-independent, OVX-induced weight gain (since they occurred after the weight gain) and cohousing with healthy mice did not have a protective effect.