Welcome to this part of our website with additional background information for doctors.
Isala is a large-scale citizen science study in which the University of Antwerp wanted to map the female microbiome in Flanders for the first time. We mainly focus on the vaginal microbiome, but for a some of the women, we also look at the microbiome of the skin around the nipple, at the groin and around and in the mouth. Isala also tries actively to break certain taboos around female and vaginal health and make them more open to discussion. For more information, be sure to read our conversation starters.
The Isala project is a fundamental research project that uses citizens’ active involvement (citizen science). This also includes feedback with individual research results. One of your patients may ask for advice about her personal result. That is why we would like to provide some additional background information on this page.
Our participants were informed at various times during the study that there is no ‘diagnosis’ at any time.
Participation in Isala does in no way replace regular gynaecological monitoring. We encourage women in all our communications to contact their trusted physician if they experience any symptoms or have concerns.
This website has since become an important information point about women’s health. According to the principles of good citizen research, we try to bring quite complex scientific information in an accessible way. The information you can find here was written in addition, specifically for doctors.
What is the microbioom?
It is the collection of all micro-organisms that live on the mucosal surfaces in our body, ranging from the gut to the skin, our oral cavity, our respiratory tract and therefore also the vagina. All these micro-organisms code for many unique genes that contribute to the functioning of our body. For example, by making digestive enzymes or vitamins or molecules that can disable unwanted pathogens. Over the past 15 years, enormous progress has been made in DNA analysis techniques to map these microorganisms. Every place on the human body is characterized by a number of frequently occurring bacterial species and properties of these species. However, there is usually still a lot of variation between individuals. So far, mainly the gut microbiome has been mapped, for example in the Flemish Gut Flora project. Now Isala wants to mainly map the vaginal microbiome.
What do we already know about the vaginal microbiome?
The vaginal microbiome is obviously important for women’s health, but not only that. Their partners also benefit from a healthy microbiome. And their children too. During a vaginal delivery and birth, the bacteria from the mother’s vagina are the first bacteria that newborns encounter. The microbiome of those babies is changing rapidly on all body surfaces, but the importance of those early ‘settlers’ cannot be underestimated.
We don’t know yet where the bacteria in the vagina come from. However, the bacteria in the gut are an important source, independent of the level of hygiene. In order to properly colonize a certain place in our body, the bacteria that end up there must also be able to survive and grow well. In the vagina, the estrogen level seems to be an important factor determining which bacteria can grow well. An increase in estrogen causes an increase in the release of glycogen by vaginal epithelial cells. When there is no oxygen in the environment, the glucose from glycogen is converted into lactic acid. We call this process fermentation. Lactobacilli are experts in such fermentation reactions. Species such as Lactobacillus crispatus, Lactobacillus iners, Lactobacillus jensenii and Lactobacillus gasseri mainly appear to have a selective advantage in the vagina. Their production of lactic acid results in low vaginal acidity, especially pH 4-5. This is often seen as an indicator of a healthy vagina. But a healthy vagina is, of course, more than just lactic acid. In principle, all metabolites produced by the vaginal microbiome can influence women’s physiology and health.
When the vaginal flora is disturbed, usually due to an increase in pH, bacterial vaginosis (BV) occurs, usually characterized by fewer lactobacilli. Most estimates approximate that about 30% of women have BV. BV is often accompanied by an unpleasant-smelling vaginal discharge. Still, not all women have symptoms or are bothered by it. In BV, the vagina is usually overgrown by anaerobic microorganisms, such as Gardnerella vaginalis. There is also a more inflammatory variant, aerobic vaginitis or AV, where the total number of bacteria has decreased, accompanied by an increase in aerobic species such as Group B Streptococci (GBS, Streptococcus agalactiae). A disturbance of the vaginal flora is associated with several complications, such as an increased risk of pregnancy complications and reduced fertility.
Several studies also suggest an increased susceptibility to various urogenital diseases and sexually transmitted diseases (STDs) in BV. But there is still insufficient evidence for many of these associations that a disrupted vaginal microbiome is (partly) the cause. That is why a project like Isala is so important. It provides unique reference material of a general cross-section of the female population (note that this cross-section is not necessarily representative in every respect), including women with and without common vaginal complaints. Although the group without complaints is by far the largest.
What information do the Isala participants receive?
Each participant receives the result of the DNA sequencing of the bacteria that we found on their self-collected vaginal swab. We multiplied a piece of the 16S rRNA gene (present in all bacteria) that contains unique information about the taxonomy of the bacteria present.
But – and this is very important for you as a doctor – we cannot always determine the species and therefore certainly not the strain and virulence of the bacteria present. For example, for women who have Streptococcus, Gardnerella or Prevotella as the dominant species in their vagina, we do not know whether it is a somewhat unfavourable or potentially beneficial variant. The women who have more of these bacteria and less Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri or Lactobacillus jensenii should not immediately worry.
We usually express the composition of the microbiome in relative abundance figures. For Isala, we chose to classify women based on the most common (most abundant) bacterial species in their vagina and provide information about the other bacteria that make up the top 8 of their vaginal microbiome. After a thorough statistical and bioinformatic analysis of the data of more than 3300 women who gave a vaginal swab, we arrived at the 8 most common types in the vagina.
Important: The results do not diagnose or value judgment on the status of the participant’s female microbiome. After all, we solely performed an observational study. At this stage of the research, we haven’t even made any links to lifestyle or health indicators. The vaginal microbiome is also very dynamic. The samples were taken during the summer of 2020: there is a good chance that the composition has changed in the meantime. Vaginal types are therefore not comparable with fixed blood groups. It is best to view the analysis of the vaginal microbiome as a blood analysis of, for example, a patient’s blood values.
Of note, the sequencing does not always work either. That is no reason for women to be alarmed. This is usually due to technical problems. Because DNA sequencing is not easy peasy 😊. It is also a new tool that is still being researched into sensitivity, specificity, limit-of-detection. The method is not yet accredited compared to current diagnostic tools.
What is the Isala team working on for the future?
In the first place, we now thoroughly probe for connections between the vaginal microbiome and fertility, menstrual cycle, nutrition, hygiene, etc. We then plan several controlled intervention studies to further study and confirm possible (causal) connections. Finally, we also really want to develop microbiome therapies. That is why we also collected the pink swabs (in addition to the blue swabs for DNA sequencing): we want to grow the ‘healthiest’ lactobacilli and further develop them as innovative biopharmaceuticals. But that is research that takes a lot of years and money.