Do the microbiome and metabolites influence the development of preeclampsia?Preeclampsia (earlier known as toxaemia) is a pregnancy-related complication, which affects approximately 2–3 percent of pregnant women in Finland. Globally, more than 70,000 mothers and 500,000 babies are annually lost as a result of preeclampsia. Although preeclampsia was identified already before the Common Era, its pathogenetic mechanisms still remain unclear. Our research team is currently investigating possible associations between the human microbiome and metabolites and the pathogenesis of preeclampsia.
Writer: Elli Toivonen
Editing: Viestintätoimisto Jokiranta Oy
While the majority of its tragic outcomes occur in poor countries, preeclampsia is a cause of significant morbidity in countries with advanced healthcare as well. The disorder was identified already thousands of years ago: the pregnancy-related complication with headache, swelling and convulsions was described by Hippocrates already 400 years BCE. However, despite the numerous lines of research, the underlying causes and pathogenetic mechanisms of preeclampsia still remain unclear. Our research team is now endeavouring to find out whether the human microbiome and its metabolites might explain the pathogenesis of the disorder.
The microbial communities in the human body, also known as the microbiome, affect our immune system and metabolism. Research has shown that certain disturbances of the microbiome are associated with, for example, obesity and diabetes which, for their part, expose pregnant women to a higher risk of preeclampsia. In addition to the traditional microbiological culturing methods, microbes can be studied through new techniques, including the identification of genetic material. This allows us to discover tiny microbial populations and species that have been challenging to study by means of culturing.
We also employ metabolomics in our research. Metabolomics refers to the scientific study of the products of human cell and microbiome metabolism, or metabolites, through which the impacts of the microbiome are transmitted in the body. From the viewpoint of metabolomics, pregnancy is a period of dramatic changes: to ensure the growth and development of the foetus, the mother’s metabolism must adjust so as to support the transfer of nutrients into the foetus. One example of such a change is the onset of physiological insulin resistance during pregnancy, which may lead to the development of preeclampsia.
An individual microbiome starts to take form already during the foetal period. The route, however, is not fully known. Does the foetus receive maternal microbiome via the vagina to the uterus or through the blood circulation of the placenta? Previously, the uterus and placenta were assumed to constitute a sterile environment during pregnancy but, thanks to advanced technologies, it was possible to describe the relevant microbiome in the 2010s.
This immediately led to the desire to clarify the possible impacts of the microbiome on pregnancy-related complications. The mere existence of placental microbiome is still controversial: the samples are easily contaminated, it is difficult to collect sufficient amounts of bacteria even though the techniques are highly sensitive, and reliable repeatability has been an issue.
Our research, entitled Pre-eclamptic Microbiota and Metabolism (PREMiuM), aims at exploring in what ways pregnancies complicated by preeclampsia differ from normal pregnancies in terms of the microbiome and metabolomics of the mother and the newborn baby. Over one hundred pregnant women participated in the study in which we collected bacterial and metabolite samples from both the mother and the newborn before and after childbirth. To obtain data concerning the impacts of diet on the microbiome, we asked the mothers to report on their individual diet and dietary supplement use. The questionnaire data was combined with the clinical information on the maternal and neonatal health during pregnancy obtained from the medical records.
We also collected sterile placenta and umbilical cord samples from those caesarean deliveries where the foetal membranes had not yet ruptured. By means of these samples, we will study the presence and quality of placental microbiome.
The discovery – or lack – of microbiome disturbances related to preeclampsia will provide additional information about the pathogenetic mechanisms and underlying causes of this mysterious disorder. Modification of the microbiome as a potential treatment of, for example, obesity is a current topic of scientific research. It would be interesting to explore the impacts of such treatments on the development and progress of preeclampsia, in case our research reveals differences in the microbiome between preeclamptic and normal pregnancies.
The strength of our research team lies in its multidisciplinarity. Our group comprises experts in microbiome research, metabolomics and preeclampsia studies, together with gynaecologists who treat patients with preeclampsia in their daily clinical work. The funding granted by the Sakari Alhopuro Foundation facilitated high-quality and accurate laboratory diagnostics and provided the clinicians in our team with the opportunity to contribute to the research. This research would not have been possible without the grant funding from the Sakari Alhopuro Foundation and other foundations. We also hope that our meticulously sampled and analysed material will serve as the foundation for future research of possible links of the microbiome and metabolomics with other disorders.
MD, PhD Elli Toivonen is a Specialist in Obstetrics and Gynaecology. Currently, she serves as a clinical teacher in Tampere University, instructing medical students in obstetrics, and also practices as a gynaecologist in Tampere University Hospital and at Kauhajoki health centre. Toivonen earned her PhD degree from the University of Tampere in 2018. Her doctoral thesis on the breech presentation of the foetus focused on the mode of delivery, monitoring of the foetal heart rate and maternal childbirth experience.