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  • Krog, Maria ChristineThe Recurrent Pregnancy Loss Unit, The Capital Region, Rigshospitalet and Hvidovre Hospital, Copenhagen University Hospitals , Copenhagen, Denmark;Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet , Copenhagen, Denmark (author)

The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-05-11
  • Oxford University Press (OUP),2022
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-490962
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-490962URI
  • https://doi.org/10.1093/humrep/deac094DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:149602092URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • STUDY QUESTIONHow does hormonal contraceptive use and menstrual cycle phase affect the female microbiome across different body sites?SUMMARY ANSWERThe menstrual cycle phase, but not hormonal contraceptive use, is associated with the vaginal and oral but not the gut microbiome composition in healthy young women.WHAT IS KNOWN ALREADYWomen with low vaginal levels of Lactobacillus crispatus are at increased risk of pre-term birth, fertility treatment failure, sexually transmitted infections and gynaecological cancers. Little is known about the effect of hormonal fluctuations on other body site’s microbiomes as well as the interplay between them.STUDY DESIGN, SIZE, DURATIONThis study includes a cohort of 160 healthy young Danish women using three different contraceptive regimens: non-hormonal methods (n = 54), combined oral contraceptive (COC, n = 52) or levonorgestrel intrauterine system (LNG-IUS, n = 54). Samples were collected from four body sites during the menstrual cycle (menses, follicular and luteal phases) at Copenhagen University Hospital, Rigshospitalet, Denmark.PARTICIPANTS/MATERIALS, SETTING, METHODSThe oral, vaginal, rectal and faecal microbiomes were characterized by shotgun sequencing. Microbial diversity and community distance measures were compared between study groups, menstrual phase timepoints and body sites. All participants answered an extensive questionnaire on current health, lifestyle and sex life. Confounding factors such as smoking, BMI and diet were analysed by PERMANOVA. Plasma oestradiol and progesterone levels are correlated with microbiome composition.MAIN RESULTS AND THE ROLE OF CHANCEThe use of COC and LNG-IUS was not associated with the microbiome composition or diversity. However, increased diversity in the vaginal microbiome was observed during menses, followed by a subsequent expansion of Lactobacillus spp. during the follicular and luteal phases which correlated with measured serum oestradiol levels (r = 0.11, P < 0.001). During menses, 89 women (58%) had a dysbiotic vaginal microbiome with <60% Lactobacillus spp. This declined to 49 (32%) in the follicular phase (P < 0.001) and 44 (29%) in the luteal phase (P < 0.001). During menses, bacterial richness and diversity in saliva reached its lowest point while no differences were observed in the faecal microbiome. The microbiome in different body sites was on average more similar within the same individual than between individuals, despite phase or hormonal treatment. Only the vagina presented a clear cluster structure with dominance of either L. crispatus, Lactobacillus iners, Gardnerella vaginalis or Prevotella spp.LARGE SCALE DATAThe microbiome samples analysed in this study were submitted to the European Nucleotide Archive under project number PRJEB37731, samples ERS4421369–ERS4422941.LIMITATIONS, REASONS FOR CAUTIONThe cohort is homogenous which limits extrapolation of the effects of ethnicity and socio-economic status on the microbiome. We only present three defined timepoints across the menstrual phase and miss potential important day to day fluctuations.WIDER IMPLICATIONS OF THE FINDINGSThe use of hormonal contraception did not significantly associate with the microbiome composition in the vagina, faeces, rectum or saliva in healthy young women. This is a welcome finding considering the widespread and prolonged use of these highly efficient contraceptive methods. The menstrual cycle is, however, a major confounding factor for the vaginal microbiome. As such, the time point in the menstrual cycle should be considered when analysing the microbiome of women of reproductive age, since stratifying by vaginal dysbiosis status during menstruation could be misleading. This is the first study to confirm by direct measurements of oestradiol, a correlation with the presence of L. crispatus, adding evidence of a possible hormonal mechanism for the maintenance of this desirable microbe.

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  • Hugerth, Luisa WKarolinska Institutet (author)
  • Fransson, EmmaKarolinska Institutet (author)
  • Bashir, ZahraThe Recurrent Pregnancy Loss Unit, The Capital Region, Rigshospitalet and Hvidovre Hospital, Copenhagen University Hospitals , Copenhagen, Denmark;Department of Obstetrics and Gynecology, University Hospital Zealand, Slagelse Hospital , Slagelse, Denmark (author)
  • Nyboe Andersen, AndersThe Fertility Department Section 4071, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark (author)
  • Edfeldt, GabriellaKarolinska Institutet (author)
  • Engstrand, LarsCentre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet , Stockholm, Sweden;Science for Life Laboratory , Stockholm, Sweden (author)
  • Schuppe-Koistinen, InaKarolinska Institutet (author)
  • Nielsen, Henriette SvarreThe Recurrent Pregnancy Loss Unit, The Capital Region, Rigshospitalet and Hvidovre Hospital, Copenhagen University Hospitals , Copenhagen, Denmark;Department of Clinical Medicine, Copenhagen University , Copenhagen, Denmark;Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre Hospital , Copenhagen, Denmark (author)
  • Karolinska InstitutetThe Recurrent Pregnancy Loss Unit, The Capital Region, Rigshospitalet and Hvidovre Hospital, Copenhagen University Hospitals , Copenhagen, Denmark;Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet , Copenhagen, Denmark (creator_code:org_t)

Related titles

  • In:Human Reproduction: Oxford University Press (OUP)37:7, s. 1525-15430268-11611460-2350

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