How the Gut Microbiome Links to Menopause and Obesity, with Possible Implications for Endometrial Cancer Development

Abstract

Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and important risk factors of endometrial cancer, high estrogen levels, postmenopause and obesity. Methods: A systematic search was performed with PubMed as primary database. Three separate searches were performed to identify all relevant studies. Results: Fifteen studies were identified as highly relevant and included in the review. Eight articles focused on the relationship with obesity and eight studies focused on the menopausal change or estrogen levels. Due to the heterogeneity in patient populations and outcome measures, no meta-analysis could be performed. Both the menopausal change and obesity were noted to enhance dysbiosis by reducing microbiome diversity and increasing the Firmicutes to Bacteroidetes ratio. Both also incurred estrobolome changes, leading to increased systemic estrogen levels, especially after menopause. Furthermore, microbiome dysbiosis was reported to be related to systemic inflammation through toll-like receptor signaling deficiencies and overexpression of pro-inflammatory cytokines. Conclusions: This review highlights that the female gut microbiome is intrinsically linked to estrogen levels, menopausal state and systemic inflammation, which indicates gut microbiome dysbiosis as a potential hallmark for risk stratification for endometrial cancer. Studies are needed to further define the role the gut microbiome plays in women at risk for endometrial cancer.

Body composition and cardiometabolic health across the menopause transition

“…Investigating racial and ethnic disparities in menopause‐related health outcomes is particularly important in the quest to maximize the “health span” and not just the life‐span of women. Finally, although research is currently limited, studies of how the female gut microbiome modifies energy balance, calorie absorption, and fat storage during menopause should also be undertaken (153,154).…”

“…Investigating racial and ethnic disparities in menopause-related health outcomes is particularly important in the quest to maximize the "health span" and not just the life-span of women. Finally, although research is currently limited, studies of how the female gut microbiome modifies energy balance, calorie absorption, and fat storage during menopause should also be undertaken(153,154).The North American Menopause Society (NAMS) is a resource to assist medical professionals in the management of menopause and it provides a body of evidence-based recommendations for the clinical care of women across the menopause transition(17).These recommendations range from managing common body changes (particularly weight gain) and disease risk to complementary and alternative medicine and prescription-based treatment approaches. If weight loss is indicated (i.e., BMI ≥ 30kg/m 2 or BMI ≥27 kg/m 2 with a comorbidity), NAMS recommends combining caloric restriction alongside an intensive behavioral lifestyle intervention (≥14 in-person counseling sessions in 6 months)(17,155).…”

Staphylococcus aureus-Derived Extracellular Vesicles Enhance the Efficacy of Endocrine Therapy in Breast Cancer Cells

“…Staphylococcus is a bacterium that produces β−galactosidase [ 12 ]. It is abundant in elderly, healthy controls but almost absent in breast cancer patients ( Figure 3 ).…”

“…Alpha and beta diversity of microbiome assemblages were analyzed at the genus level. Estrobolomes from previous studies ( Table 1 ) [ 10 , 12 ] were used for comparison.…”

“…The estrogen−metabolizing microbiome is known as the estrobolome [ 10 ]. It regulates the levels of estrogen circulating in the human body [ 11 ] and is related to the development and progression of various carcinomas, including breast cancer [ 12 ]. More than 70% of all breast cancers are hormone receptor−positive breast cancers [ 13 ], and elevated estrogen levels are a risk factor for breast cancer development [ 14 ].…”