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The Relationship of the Intestinal Microbiome and the Menstrual Cycle

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ClinicalTrials.gov Identifier: NCT03581201
Recruitment Status : Recruiting
First Posted : July 10, 2018
Last Update Posted : July 10, 2018
Sponsor:
Collaborator:
University of Vienna
Information provided by (Responsible Party):
Alexandra Kautzky-Willer, Medical University of Vienna

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.

Condition or disease Intervention/treatment
Sex Hormones Microbial Colonization Diagnostic Test: Laboratory measurements Diagnostic Test: Stool samples Diagnostic Test: Bioimpedance analysis

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.


Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Relationship of the Intestinal Microbiome and the Dynamic Changes of Sex Hormone Concentrations in Women at Childbearing Age
Estimated Study Start Date : July 18, 2018
Estimated Primary Completion Date : June 13, 2019
Estimated Study Completion Date : July 1, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Oral contraception
Healthy females at childbearing age with oral contraception.
Diagnostic Test: Laboratory 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 Test: Stool 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 Test: Bioimpedance analysis
The Bioimpedance analysis (BIA) is used for the measurement of body composition and will be done at every study visit.

No contraception
Healthy females without any contraception at all.
Diagnostic Test: Laboratory 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 Test: Stool 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 Test: Bioimpedance analysis
The Bioimpedance analysis (BIA) is used for the measurement of body composition and will be done at every study visit.




Primary Outcome Measures :
  1. Changes of the B-Glucuronidase, expressed by the intestinal microbiome, during the menstrual cycle in women at childbearing age [ Time Frame: 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 Outcome Measures :
  1. Changes of the Beta-Glucuronidase during the menstrual cycle in women with oral contraception [ Time Frame: Up to 7 weeks ]
  2. Changes of the Beta-Glucuronidase during the menstrual cycle in women without any contraception [ Time Frame: Up to 7 weeks ]
  3. Changes of the intestinal microbiome during the menstrual cycle in women at childbearing age with- and without contraception [ Time Frame: Up to 7 weeks ]
  4. Relationship of the β-Glucuronidase with the changes of the female sex hormones during the menstrual cycle in women at childbearing age. [ Time Frame: Up to 7 weeks ]
  5. Relationship of the intestinal microbiome with the changes of the female sex hormones during the menstrual cycle in women at childbearing age. [ Time Frame: Up to 7 weeks ]


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
In total, 20 patients (10 subjects with oral contraceptives and 10 subjects without oral contraceptives or any contraceptive at all) between 18 and 40 years and a body mass index (BMI) between 18 and 24 kg/ m² will be examined in this study.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03581201


Contacts
Contact: Alexandra Kautzky-Willer, Prof. Dr. +434040021260 alexandra.kautzky-willer@meduniwien.ac.at
Contact: Michael Leutner, Dr.med.univ., PhD, MSc michael.leutner@meduniwien.ac.at

Locations
Austria
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Alexandra Kautzky-Willer, Univ.Prof.Dr.    +434040021260    alexandra.kautzky-willer@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
University of Vienna
Investigators
Principal Investigator: Alexandra Kautzky-Willer, Prof. Dr. Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna

Responsible Party: Alexandra Kautzky-Willer, Univ. Prof. Dr., Head of the Gender Medicine Unit, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03581201     History of Changes
Other Study ID Numbers: MB2018
First Posted: July 10, 2018    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexandra Kautzky-Willer, Medical University of Vienna:
intestinal microbiome
oral contraceptives
estrogens
bacterial population
hormone status
glucose profiles
lipid parameters
body composition

Additional relevant MeSH terms:
Communicable Diseases
Infection
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs