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

Project Information

HEROINE

Grant agreement ID: 101039493

DOI

10.3030/101039493

EC signature date 1 February 2022

Start date 1 June 2022

End date 31 May 2027

Funded under

• European Research Council (ERC)

Total cost

€ 1 499 485,00

EU contribution

€ 1 499 485,00

Coordinated by

TECHNISCHE UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 1 - HEROINE (Hormone-microbiome interactions as a key-player in female health)

Reporting period: 2022-06-01 to 2024-11-30

Summary of the context and overall objectives of the project

Incidence rates of inflammatory and autoimmune diseases are increasing dramatically and are often much higher in women. Hormones are hypothesized to play a central role in this sex bias. At the same time, the microbes that live in and on our body are often linked to disease pathology. Microbes are capable of producing hormone-like signals, can metabolize hormones and regulate their production, while hormones can influence bacterial growth. However, a key understudied aspect is the interplay between hormones and microbes in the human body and the role of these interactions in human health and disease.

In women in particular, hormones fluctuate throughout the menstrual cycle and are commonly used as drugs. However, this information is often not collected or taken into consideration in microbiome studies. As part of HEROINE, we investigate how exogenous and endogenous sex hormones affect the female microbiome and the role of hormone-microbiome interactions in female health. More specifically, hormonal contraceptives artificially inhibit natural hormonal fluctuations during the menstrual cycle, while hormone levels naturally cease to fluctuate after menopause. Here, we will identify how these endocrine changes impact the gut microbiome and how they are linked to common side effects. Importantly, hormonal imbalances can lead to infertility. Using female infertility as a model system for hormonal imbalance, we are investigating microbial factors that are linked to infertility and will determine how they disrupt or are disrupted by hormones.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project, we establish two female cohorts with detailed information on menstrual cycle and hormone levels. State-of-the-art multi-omics data are being generated and integrated, including metagenomics data and high-resolution metabolomics data with a focus on estrogen. Furthermore, we are developing pipelines combining sequence similarity and structure-based screening of genes to identify potential bacterial candidate genes involved in microbial metabolism of sex hormones. A first set of promising candidate genes are being moved to experimental follow-up investigation, using strains isolated from patient samples.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The established cohorts and isolated bacterial strains form an important resource to investigate the role of the microbiome in female health. As part of this, we are investigating gut and vaginal microbiome changes associated with hormonal fluctuations in healthy women and investigate their role in female infertility. Importantly, the tools and approaches that we are developing, will also be applicable to other research questions aiming to identify and investigate host-microbial interactions in health and disease.

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