CTMR research in women’s reproductive health
Our research aims to describe the microbiome in healthy women of reproductive age as well as in pregnant women and investigates associations between the vaginal microbiota and the risk for diseases, such as HPV infection or pregnancy complications. We are starting to understand more about the importance of the microbiota for women’s health and include gut and oral sampling in our studies.
- What composition of the vaginal microbiome is normal in healthy women, i.e. during the menstrual cycle?
- What is the composition of the healthy vaginal, oral and faecal microbiota of pregnant and postpartum women?
- Can certain compositions of the vaginal microbiota be associated to symptoms of bacterial vaginosis or to HPV infections?
- Can preterm birth or other adverse pregnancy conditions be predicted by the microbiota composition?
- Is the placenta harbouring a microbiome or is it sterile?
- What characterize the microbiota in endometriosis and in recurrent pregnancy loss?
- Is the microbial composition (vaginal/intestinal and oral) during pregnancy associated with current depressive symptoms or with postpartum depression?
- How do commonly prescribed drugs, diet and other factors affect the (vaginal) microbiome composition and function, and how does this affect female health?
SweMaMi – Swedish Maternal Microbiome project
The currently ongoing SweMaMi study aims to assess the association between the maternal microbiota during pregnancy and post-partum and the risk of maternal and neonatal adverse events. The study will recruit 2500 pregnant women in Sweden. The research questions regarding the microbiota overlap with those from the BASIC study, but in the SweMaMi project there is a larger study population recruited from all over Sweden. Participating women are asked to complete three comprehensive online questionnaires on general health, prior medical and reproductive history, drug use, lifestyle, diet and mental health. Participants provide microbiota samples from the vagina, oral cavity and gut (faecal) at gestational week 17–19 and 28–30, and at 6–10 weeks after the expected delivery date. A faecal sample from the new-born is also collected. The primary goal is to investigate associations between the microbiota profiles and preterm birth (PTB) and other pregnancy complications.
BASIC: associations between microbiota and preterm birth (and depression)
The BASIC study began in 2010 in Uppsala, and more than 6000 pregnancies have so far been included. Microbiota samples are being collected since 2016 at two time points during the course of pregnancy, during the delivery and once during the postpartum period; gestational week 17–19 and 30-32 and at 6–10 weeks after the delivery date. The research questions overlap with the SweMaMi study, but the overall aim of the BASIC regards perinatal depression and its potential biological correlates. Mothers are therefore also asked to provide blood samples for analysis of i.e. markers of inflammation
PlaMi – Placental Microbiome study: does microbiome acquisition start in utero?
The PlaMi study aims to address a subject of much current debate in the scientific community relating to whether the placenta hosts microbiota. Positive reports on this have appeared in the public domain (Chen et al. 2017; Aagaard et al. 2014); however, these findings are also contested and believed to be due to contamination during the sampling procedure. The observation of a placental microbiome contributes to the interesting question of when the acquisition of microbiota begins, and, as has been proposed, is an infant’s microbiota more similar to the mother’s oral microbiota than her vaginal or faecal microbiota? The PlaMi study therefore collected samples from healthy 50 women with a planned C-section and 25 with a normal vaginal delivery. Samples were taken from 3 locations of the placenta, amniotic fluid, umbilical cord blood, vernix, vagina, saliva and faces at delivery.
VaMiGyn –Vaginal Microbiota in Gynaecological health
The VaMiGyn study aims to define the vaginal microbiota in healthy women of fertile age, in order to provide cross-sectional data that will be used as a baseline for other studies. This study takes advantage of the national cervical cell screening program in Sweden. All women between 23 and 60 years who are called for screening receive an information letter about the study and are asked if they are willing to fill in a questionnaire and give a vaginal swab when they come for screening. A total of 2500 women undergoing HPV screening in Uppsala will be recruited, with vaginal microbiota samples collected from all participants, and a faecal and oral sample from a subset of 500. Variation of the microbiota that is associated with HPV infection, HPV subtypes, HPV vaccination, as well as antibiotic usage, is investigated and women with pre-states of cervical cancer are sampled consecutively. The VaMiGyn study is planned for completion in 2019.
MiMens – Microbiome dynamics during the menstrual cycle
The MiMens study aims to describe the vaginal microbiota in relation to the menstrual cycle in healthy women, to provide baseline data on changes in microbiota during the cycle. Three groups of each 50 healthy female volunteers have been recruited, and selected based on a regular menstrual cycle, and no use of hormonal contraception, oral contraceptive or the levonorgestrel intrauterine system. The participants have completed three visits over 6 weeks. During the study, the women have collected daily vaginal swabs, with salivary, urinary, faecal and blood samples given at study visits. Endometrial samples were also collected at some visits. The participants have undergone a gynaecological investigation and kept a diary of intercourse, bleeding etc., and completed a questionnaire on general health, prior medical and reproductive history, lifestyle, diet and mental health.
ACHVAM - Vaginal microbiota culture system
Most studies on microbiome (genomes of the microbiota) are conducted on intestinal microbiota. Studies on genital microbiome systems have still not been as properly characterized as the gut microbiota. A growing body of evidences suggests that the microbiome in genital tracts play important roles in modulating our health, however, there is no system that allows us to culture genital microbiota in vitro, which limited further mechanism studies on genital microbiota. The aim of this project is to build up a platform to culture vaginal microbiota from both Lactobacillus dominated and non-dominated individuals. Different culture media and conditions will be checked for genital microbiota growth in order to develop the best medium for bacteria in the genital tract, suitable for maintaining the balance of existing bacteria through time.
MiRPL: Microbiota and recurrent pregnancy loss
The MiRPL study in Copenhagen investigates the microbiota profile of women with unexplained recurrent pregnancy loss. The hypothesis is that a specific composition of microbiota is present in women with immune-mediated recurrent pregnancy loss, reflecting an unbalanced immune system. The study will look at the microbiota of the gut, mouth, vagina and endometrium in relation to pregnancy outcome and long-term prognosis, with samples taken at various time-points including prior to pregnancy, early pregnancy (gestational age 6–8 weeks), pregnancy loss or second trimester gestational age 12–14 weeks.
MiEndo: Microbiota in Endometriosis
The MiEndo study aims to compare and describe the microbiota composition in the gut, mouth, vagina, peritoneum (at operation) and in the endometriosis plaques and endometrium of women with endometriosis in relation to grade of disease, pain, quality of life and success of operation.
The study will recruit 100 women at Rikshospitalet, Copenhagen with moderate to severe disease and 20 patients with intestinal resection due to intestinal disease.
- Professor Matts Olovsson, Uppsala University
- Professor Alkistis Skalkidou, Uppsala University
- Lektor, överläkare Eva Wiberg Itzell, Karolinska Institutet
Assessment of In Vitro and In Silico Protocols for Sequence-Based Characterization of the Human Vaginal Microbiome
Luisa W. Hugerth, Marcela Pereira, Yinghua Zha, Maike Seifert, Vilde Kaldhusdal, Fredrik Boulund, Maria C. Krog, Zahra Bashir, Marica Hamsten, Emma Fransson, Henriette Svarre-Nielsen, Ina Schuppe-Koistinen, Lars Engstrand
Vaginal microbiota and human papillomavirus infection among young Swedish women
Liqin Cheng, Johanna Norenhag, Yue O. O. Hu, Nele Brusselaers, Emma Fransson, Andreas Ährlund-Richter, Unnur Guðnadóttir, Pia Angelidou, Yinghua Zha, Marica Hamsten, Ina Schuppe-Koistinen, Matts Olovsson, Lars Engstrand & Juan Du
npj Biofilms and Microbiomes (2020)
No evidence for a placental microbiome in human pregnancies at term.
Sterpu I, Fransson E, Hugerth LW, Du J, Pereira M, CHENG L,Radu SA, Calderón-Pérez L, Zha Y, Angelidou P, Pennhag A, Boulund F, Scheyniusa, Engstrand L, Wiberg-Itzel E, Schuppe-Koistinen I
American Journal of Obstetrics and Gynecology (2020)
The reproductive microbiome - clinical practice recommendations for fertility specialists.
García-Velasco JA, Budding D, Campe H, et al.
Reprod Biomed Online. 2020;41(3):443-453.
The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis.
Norenhag J, Du J, Olovsson M, Verstraelen H, Engstrand L, Brusselaers N
BJOG 2019 Jun;():
Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis.
Brusselaers N, Shrestha S, van de Wijgert J, Verstraelen H
Am. J. Obstet. Gynecol. 2019 Jul;221(1):9-18.e8
Inflammatory markers in women with postpartum depressive symptoms.
Bränn E, Fransson E, White RA, Papadopoulos FC, Edvinsson Å, Kamali-Moghaddam M, et al
J. Neurosci. Res. 2018 Sep;():.
Changes in Cervical Human Papillomavirus (HPV) Prevalence at a Youth Clinic in Stockholm, Sweden, a Decade After the Introduction of the HPV Vaccine.
Ährlund-Richter A, Cheng L, Hu YOO, Svensson M, Pennhag AAL, Ursu RG, et al
Front Cell Infect Microbiol 2019 ;9():59