Date

2017

Department or Program

Biological Chemistry

Primary Wellesley Thesis Advisor

Vanja Klepac-Ceraj

Additional Advisor(s)

Donald Elmore

Additional Advisor

Louise Darling

Additional Advisor

Selwyn Cudjoe

Abstract

Post-menopausal women have an increased risk of developing metabolic disorders, such as obesity and type-two diabetes. Estradiol, a type of estrogen, which is primarily produced by ovaries and declines in postmenopausal women, protects against diet-induced obesity in women and female mice. However, the mechanisms by which estradiol prevents diet-induced obesity are not completely understood. Host diet has been shown to shift the compositional pattern of the gut microbiota­, and both diet and the gut microbiome have been linked to weight gain and obesity. We hypothesized that one mechanism by which estradiol-treated mice resist diet-induced weight gain is through the gut microbiota. For my thesis, I investigated the effects of estradiol on the gut microbiota to a diet change and analyzed the fecal gut microbiota from fourteen adult C57BL6 mice that were ovariectomized and subcutaneously implanted with capsules containing either 17β-estradiol (E2) or oil (vehicle; control; Veh). All mice were fed a standard rodent diet for 10 days and then switched to a high-fat diet (HFD) for 25 days. To identify and compare microbial community composition of samples across treatments, we analyzed the longitudinal 16S rRNA gene data from fecal pellets. I observed that E2 treatment altered the gut microbiota response and structure following the diet change. Specifically, the gut microbiota in E2 mice response to the diet change was attenuated compared to the Veh mice. Moreover, HFD-fed mice were characterized by increased relative abundances of Firmicutes and Proteobacteria, but these HFD-induced shifts were conservative for the E2-treated group. With the diet change and the lack of E2 treatment, fecal endotoxin levels and taxa associated with inflammatory and metabolic diseases increased greatly, such as Helicobacter and Peptostreptococcaceae. Comparatively, the diet change had no effect on endotoxin levels and induced slight increases in abundance of these inflammatory and metabolic disease associated taxa in E2 mice. Microbes characterized as metabolizers of plant-based diets, such as Ruminococcaceae and S24-7, were, however, associated with and in higher abundance in E2 mice than Veh mice during HFD. In summary, HFD disturbs the gut microbiota diversity and composition, but the HFD associated changes are lessened with E2 treatment. The reduced response and alterations in the gut microbiota to dietary change in E2 mice may be a critical component in understanding the complexities by which estradiol protects against obesity.

Supplementary_Table_1.pdf (30 kB)
Supplementary Table 1

Available for download on Sunday, April 21, 2019

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