Surgical Menopause and Estrogen Therapy Modulate the Gut Microbiota, Obesity Markers, and Spatial Memory in Rats

Abstract

Menopause in human females and subsequent ovarian hormone deficiency, particularly concerning 17β-estradiol (E2), increase the risk for metabolic dysfunctions associated with obesity, diabetes type 2, cardiovascular diseases, and dementia. Several studies indicate that these disorders are also strongly associated with compositional changes in the intestinal microbiota; however, how E2 deficiency and hormone therapy affect the gut microbial community is not well understood. Using a rat model, we aimed to evaluate how ovariectomy (OVX) and subsequent E2 administration drive changes in metabolic health and the gut microbial community, as well as potential associations with learning and memory. Findings indicated that OVX-induced ovarian hormone deficiency and E2 treatment had significant impacts on several health-affecting parameters, including (a) the abundance of some intestinal bacterial taxa (e.g., Bifidobacteriaceae and Porphyromonadaceae), (b) the abundance of microbial short-chain fatty acids (SCFAs) (e.g., isobutyrate), (c) weight/BMI, and (d) high-demand spatial working memory following surgical menopause. Furthermore, exploratory correlations among intestinal bacteria abundance, cognition, and BMI underscored the putative influence of surgical menopause and E2 administration on gut-brain interactions. Collectively, this study showed that surgical menopause is associated with physiological and behavioral changes, and that E2-linked compositional changes in the intestinal microbiota might contribute to some of its related negative health consequences. Overall, this study provides novel insights into interactions among endocrine and gastrointestinal systems in the post-menopausal life stage that collectively alter the risk for the development and progression of cardiovascular, metabolic, and dementia-related diseases.

The impact of herbal medicine in regulating intestinal flora on female reproductive disorders

“…The intestinal flora is involved in the development of IR, T2DM by influencing the levels of metabolites (Canfora et al, 2019). The composition of the intestinal flora and the abundance of SCFAs that can be observed in ovariectomized constructs of menopausal rats significantly alter the overall health of the menopausal rats (Zeibich et al, 2021). Multiple lines of evidence suggest that the intestinal flora plays an important role in the development of POI and may influence autoimmune dysfunction (De Luca and Shoenfeld, 2019), bone health (Ibanez et al, 2019), and cognitive and neurological health (Martin et al, 2018).…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…Estrogen inhibits 11β -hydroxysteroid dehydrogenase type 1, an enzyme involved in the synthesis of bioactive glucocorticoids from its inactive precursor. Estrogen-mediated neuroprotection also interconnects with the IGF-1 signaling pathway ( 90 ). Peripherally, either HPA axis imbalance, islet dysfunction or HPA axis imbalance can affect intestinal flora balance and promote chronic expression of peripheral inflammatory markers ( 91 , 92 ) (Blue circle in Figure 1 ).…”

Supplementation of Clostridiales affects microbial profile and induces sex- specific social behavior deficits in mice following prenatal immune insult

“…However, rodent models that are used to investigate underlying etiology of autism spectrum disorders have historically been performed with predominantly male cohorts, and only recent research has attempted to overcome this bias by including female mice in studies and accounting for sex differences [20]. Because of the known sexual dimorphism of many neurodevelopmental conditions and in uence of sex hormones on the gut microbiota, it is critical to remedy the lack of female inclusion in rodent studies, and to assess whether the gut microbiota-sex interplay can differentially impact observed phenotypes [21][22][23].…”