HEROINE · Hormone-microbiome interactions as a key-player in female health

Incidence rates of inflammatory and autoimmune diseases are increasing dramatically and a clear sex bias exists in disease presentation and progression. While the underlying reasons are largely unknown, hormones are hypothesized to play a central role in these discrepancies and the microbiome is linked to disease pathology. However, a key understudied player is the interplay between hormones and the microbiome in human health.Crucially, hormone-microbiome interactions in the human body are poorly understood. Microbes produce hormone-like signals and play a role in hormone metabolism and regulation, while hormones influence bacterial growth. It is currently unknown how the menstrual cycle impacts the microbiome and how disruptions of this natural cycle impact female health. I have identified unique fluctuations in microbial diversity in healthy women that are absent in men and altered in women on hormonal contraceptives. There is a lack of medical research focusing on female physiology, particularly investigating endocrinological changes and disruptions. Understanding the consequences of endocrine-related disruptions and how hormone-microbiome interactions contribute to them is a fundamental step towards precision medicine that will benefit both women and men.Therefore, I will systematically investigate hormone-microbiome interactions in (1) healthy women on and off hormonal contraceptives, (2) women at menopause and (3) infertile women receiving fertility treatment. I will integrate clinical data with state-of-the-art multi-omics profiles using computational approaches and I will combine these with mechanistic validation using bacterial strains isolated from the female subjects. At the end of my project, we will know how exogenous and endogenous hormones interact with the microbiome and how they impact female health. Further, we will identify biomarkers for optimal treatment of infertility and propose new microbiome-based therapeutic strategies for this disorder.