Tetel, Marc J.

Abstract Disclosure: A. Zhang: None. J. Kapoor: None. C. Deveney: None. A.G. Cope: None. M.M. Walther-Antonio: None. N. Chia: None. C.W. Pattanayak: None. M.J. Tetel: None. The vaginal microbiome (VM) consists of the microorganisms and their metabolites residing in the vaginal tract and is critical for maintaining female reproductive health. The Lactobacillus species predominate most VMs and produce lactic acid, which has been cited as a key protector of vaginal health. Alterations in the finely balanced vaginal microbiome can cause infections, such as bacterial vaginosis, and may contribute to the development of endometrial and ovarian cancer. While it is well-established that stress and the gut microbiome impact each other via the gut-brain axis, the influence of stress, hormones, and lifestyle factors on the VM composition remains poorly understood. We investigated the relationship between stress, hormones (menstruation, hormonal contraception), lifestyle factors (diet, exercise, sleep), and the VM composition. In this 10-week study, healthy, young female volunteers (n=62) provided daily vaginal and fecal swabs, weekly stress ratings, daily data on sleep and activity (via FitBit) and diet information. High-throughput 16S rRNA sequencing was used to identify the vaginal microbial composition of each sample. Types of hormonal birth control were none (n=30), local progestin (n=9), systemic progestin-only (n=7), or systemic estrogens and progestin combined (n=16). Consistent with our previous study, vaginal microbial diversity, as measured by the Shannon index, varied by type of hormonal birth control, with participants not on hormonal birth control having the highest average diversity. There was a positive relationship between average stress and vaginal microbial diversity, with preliminary results suggesting that this relationship depends on hormonal birth control status. Participants who menstruated during the 10-week study had a higher vaginal microbial diversity than those who did not. We are currently analyzing which microbes contribute to these differences in vaginal microbial diversity. Microbiota and fungal data from the daily vaginal and fecal swab samples will be analyzed to determine how stress, hormones and/or lifestyle factors relate to crosstalk between the vaginal and gut microbiomes. These findings may provide long-term, time-longitudinal insights into how these two important microbiomes are involved in important aspects of women’s health. Presentation: Sunday, July 13, 2025

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

The vaginal microbiome is a critical component of women’s sexual and reproductive health, with variations in microbial composition, particularly the loss of Lactobacillus species, being implicated in gynecologic and obstetric diseases. Given that the vaginal microbiome is so crucial, why do vaginal microbial profiles vary strikingly from person to person and even change over time within the same person? In the present study, which tracked the daily vaginal microbiomes of young healthy women through different lifestyles, we found that use of a locally released progestin contraceptive, a vegetarian diet, and intense exercise appear to lead to vaginal microbiome alterations and loss of Lactobacillus species. The impact of these vaginal microbiome changes on immediate and long-term health remain to be investigated.