E2 dose on microbiome rat model

A decline in estradiol (E2) production during menopause has been associated with weight gain and memory changes. These comorbidities have been linked with disturbances in the gut microbiome. We hypothesized that E2 regulates the gut microbiome in a dose-dependent manner, and that E2-dependent changes in the gut microbiome are linked to menopausal comorbidities. We characterized gut microbiome composition using 16S rRNA gene sequencing, quantified host body weight and memory scores in middle-aged ovariectomized (OVX) rats that received Vehicle, Low-E2, or High-E2 treatments. E2 significantly altered gut microbiota composition in mucosal and luminal space of proximal and distal regions of the colon. Relative abundance of Turicibacter, Bifidobacterium, and Allobaculum, as well as predicted abundances of genes involved in E2 deconjugation, beta-glucuronidase and beta-glucosidase, increased with E2 dose. The Vehicle group had significant weight gain compared to E2-treated groups. Body-weight positively correlated with Lactobacillus and negatively with Turicibacter abundance. Although E2 treatment did not alter spatial working memory load performance, gut microbiome composition correlated with the memory errors independently from the E2 dose. In summary, E2 dose-dependently altered fecal and mucosal microbiota throughout the colon, suppressed weight gain, and was correlated with cognitive benefits through manipulation of complex gut microbiota-host physiology interactions.