Sex Hormones, Microbial Colonization
Conditions
Keywords
intestinal microbiome, oral contraceptives, estrogens, bacterial population, hormone status, glucose profiles, lipid parameters, body composition
Brief summary
In the present study the dynamic changes of the intestinal microbiome are observed over a 4-week period in the different stages of the menstrual cycle in women at childbearing age. The focus is on how the dynamic changes of sex hormones during a menstrual cycle of women at childbearing age (with or without contraception) are related to microbiological colonization of the gut. In Addition the Expression of the β-glucuronidase by the bacteria will be investigated.
Detailed description
Our gut has a complex and diverse bacterial population which is called the microbiome. The number of bacteria in the intestine is estimated to exceed 10\^14. The composition of the microbiome is individual and changes over the lifetime of the host. The composition of a healthy microbiome consists more than 90% of bacteria from the Bacteroidetes and Firmicutes phyla types. Nevertheless the microbiome varies even between healthy individuals and evolves over the lifetime. Most of the microorganisms are not pathogen, thus they have been shown to interact with several physiological processes in our body. In Addition it has been shown that the bacterial population has an impact on building our gut epithelial cells, our immunology and the defence against pathogens. Interestingly estrogen and the microbiome seem to be under reciprocal influence. In our body estrogen is only active in the deconjugated form. Therefore, after it was conjugated in the liver, the bacteria in the gut can perform a deconjugation through the secretion of the enzyme ß-glucuronidase. Ultimately, the activated estrogen is going back into blood circulation, otherwise it would leave the body through bile excretion. The composition of the microbiome is fundamental, because the presence and abundance of different gene expressions varies between the different types of bacteria. The bacterial genes which are responsible for metabolizing estrogens are called the estrobolome. However, data whether there is a relationship of the changes of the sex hormones during the menstrual cycle and the intestinal microbiome in women is sparse. Parts of the estrogens circulating in the body are metabolised in the liver and are then secreted to the intestine conjugated with glucuronide. The intestinal microbiota could potentially affect estrogen metabolism via Beta-glucuronidase activity. Beta-glucuronidase is an enzyme that catalyses the deconjugation of estrogen. As a consequence, it may bind to estrogen receptors and unfold its downstream effects.
Interventions
DIAGNOSTIC_TESTLaboratory measurements
Laboratory measurements will be collected every week during the Duration of one menstrual cycle and includes the following: * Hormone analysis * Clinical chemistry * Complete blood count * Adipokines * Glucose and HbA1c-levels * Urinary Chemistry
DIAGNOSTIC_TESTStool samples
For a Duration of one menstrual cycle the study participants will be instructed to collect stool samples every two days. The investigation of the intestinal microbiome will be done by sequencing the 16S rRNA gene.
DIAGNOSTIC_TESTBioimpedance analysis
The Bioimpedance analysis (BIA) is used for the measurement of body composition and will be done at every study visit.
Sponsors
University of Vienna
Medical University of Vienna
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* women at childbearing age * age 18-40 years * BMI 18.5-24.9 kg/m² * taking oral contraceptives * not having any contraceptives
Exclusion criteria
* chronic and acute infectious diseases * history of taking antibiotics or probiotics in the last 3 months * gastrointestinal disorders in the last 3 months * Polycystic Ovary Syndrome * disorders of the menstrual cycle (e.g. oligomenorrhea, anovulation) * other than mediterranean diet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the B-Glucuronidase, expressed by the intestinal microbiome, during the menstrual cycle in women at childbearing age | Up to 7 weeks | Parts of the estrogens circulating in the body are metabolised in the liver and are then secreted to the intestine conjugated with glucuronide. The intestinal microbiota could potentially affect estrogen metabolism via β-glucuronidase activity. β-glucuronidase is an enzyme that catalyses the deconjugation of estrogen. As a consequence, it may bind to estrogen receptors and unfold its downstream effects. RNA and total DNA will be extracted from the fecal samples and microbiome community composition will be assessed by sequencing the 16s ribosomal RNA gene. Then reverse transcription of the total RNA and targeted amplification and sequencing of β-glucuronidase gene fragment will be applied in order to find out which bacteria are producing the β-glucuronidase enzyme. Furthermore, the enzymatic activity in the samples will be measured using the β-glucuronidase colorimetric assay with p-nitrophenol glucuronide. |
Secondary
| Measure | Time frame |
|---|---|
| Changes of the intestinal microbiome during the menstrual cycle in women at childbearing age with- and without contraception | Up to 7 weeks |
| Relationship of the β-Glucuronidase with the changes of the female sex hormones during the menstrual cycle in women at childbearing age. | Up to 7 weeks |
| Relationship of the intestinal microbiome with the changes of the female sex hormones during the menstrual cycle in women at childbearing age. | Up to 7 weeks |
| Changes of the Beta-Glucuronidase during the menstrual cycle in women with oral contraception | Up to 7 weeks |
| Changes of the Beta-Glucuronidase during the menstrual cycle in women without any contraception | Up to 7 weeks |
Countries
Austria
Contacts
Primary ContactAlexandra Kautzky-Willer, Prof. Dr.
Backup ContactMichael Leutner, Dr.med.univ., PhD, MSc
Outcome results
None listed