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 3-5 weeks after OVX which was subsequent to the weight gain that occurred 2 weeks post-surgery. 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 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.

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

“…Ten taxa were increased during STND compared to HFD, including Turibacteriales (class), its family Turibacteriaceae and the genus Turibacter, as reported previously [49]. The relative abundances of the family Clostridiaceae and its genus Clostridium and Coprococcus were also increased during STND compared to HFD.…”

“…Similarly, in a PCOS mouse model, FMT from androgen-treated mice disrupts metabolic and endocrine health in germ-free recipients, whereas gut microbiota from control donors protects against metabolic dysregulation [ 60 , 61 , 62 ]. In a different study, diet-independent, ovariectomy-induced weight gain was not rescued by cohousing with intact mice, with the goal of transferring of gut microbiota [ 49 ]. It is possible that a more complete transfer of microbiota is needed to rescue this ovariectomy-induced weight gain, such as fecal microbiota transfer (FMT) by gavage or co-housing combined with FMT.…”

Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet

“…It is important to note that gut microbiota elicits a variety of responses based on the factors contributing to metabolic disorders. For example, a transfer of healthy microbiota attenuated body weight gain and improved insulin response in PCOS models of female mice) ( 60 ), whereas did not prevent ovariectomy-dependent obesity ( 67 ). Most importantly, the present findings provide a compelling justification for further investigation of sex differences in basic and clinical studies in the function of gut microbiota in metabolic health.…”

From Menopause to Neurodegeneration—Molecular Basis and Potential Therapy

“…Soy isoflavones, which exhibit estrogen-like properties, can significantly change the fecal bacterial community in postmenopausal women [99]. In ovariectomized mice, ovariectomy was associated with a shift in the beta diversity of the gut microbiota analyzed by 16S rRNA gene sequence analysis [100]. A recent study showed that Verrucomicrobia and Actinobacteria were significantly increased in ovariectomized mice compared with a control group [101].…”