On May 23 2022, Janneke van de Wijgert, professor of infectious and immune mediated disease epidemiology at UMC Utrecht, held her inaugural lecture. In this lecture, Janneke discussed the female microbiome: the ‘community’ of microorganisms found in the female genital and urinary tracts. A striking statement in Janneke's lecture is that – in her opinion – the quality of scientific microbiome research is rather variable. The quality of microbiome studies should be improved to move the field forward from exploration to application.

A microbiome is a community of microorganisms that live together in a certain environment (for example, in the gut or in the vagina). When the microbiome is in balance it ensures that the environment is optimal. However, an unbalanced microbiome can contribute to the occurrence of disease and other complications.

Lactic acid bacteria

Throughout much of her career, Janneke van de Wijgert studied the cervicovaginal and urinary microbiome in women in collaboration with various research institutions. In healthy women, both environments contain various lactobacillus species that produce lactic acid and antimicrobial compounds. Lactobacillus crispatus in particular is an efficient producer. As a result, other microorganisms have difficulty establishing themselves in these organs. However, in a form of dysbiosis called bacterial vaginosis, the microbiome consists of a diverse and dense community of different bacteria that cannot tolerate oxygen such as Gardnerella and Prevotella species. Another type of dysbiosis is caused by bacteria that can tolerate different levels of oxygen such as Streptococcus species and Escherichia coli. The latter is especially notorious for causing urinary tract infections.

Complications

Dysbiosis in the genital or urinary tract can cause complications. Potentially harmful vaginal bacteria can enter the uterus, fallopian tubes, or abdominal cavity through the cervix, and potentially harmful urinary tract bacteria can enter the kidneys or blood stream. This can cause the life-threatening diseases pelvic inflammatory disease and sepsis. Dysbiosis has also been linked with acquisition of sexually transmitted pathogens, including HIV and human papillomaviruses that can cause cervical cancer. In addition, bacteria associated with dysbiosis can cause infertility - and in pregnant women - miscarriage or premature birth. In the urinary tract, they can cause kidney stones, incontinence, and bladder cancer.

Watch here the inaugural lecture by prof. Janneke van de Wijgert (in Dutch language, automatic translation into English available via YouTube 'settings')

Diagnosis and treatment

According to Janneke, it is still difficult to properly diagnose a persistently unbalanced genitourinary microbiome. However, the required knowledge and technologies to improve diagnostic practices do exist. Relatively new point-of-care tests that can identify the genetic material of multiple microorganisms in one sample are a good start, but need to be better tailored to clinical practice. In addition, there is a need for inexpensive but accurate tests that physicians, nurses or patients can easily perform themselves. Although antibiotic treatment can suppress dysbiosis, this does not automatically mean that a balanced microbiome will return. To facilitate this, one could introduce lactic acid bacteria into the microbiome after the antibiotic treatment. Promising results have recently been achieved in this area, but much research is still needed to improve the efficacy.

"My scientific career has been rather atypical, but from the very beginning, I was drawn towards infection and immunity. Even now – more than 30 years later - I am still fascinated by these subjects" - Janneke van de Wijgert

Research

Microbiome research is the type of research that requires a multidisciplinary approach. Janneke van de Wijgert says: "Unfortunately, not all microbiome research teams are sufficiently multidisciplinary. As a result, many microbiome studies are of dubious quality. There are examples of studies with misleading results because they were not longitudinal or not sufficiently quantitative. In addition, ‘compositional data’, which is data expressed as proportions, are often interpreted as absolute quantities. Statistical testing is often too much focused on exploration and p-values, and too little on hypothesis-testing, taking microbiological properties such as pathogenicity and behavior within bacterial communities into account. For example, I think that it may have added value to analyze bacteria that always live together in a community – such as BV-anaerobes – as a group and not only as many different individuals. Finally, many microbiome studies do not sufficiently incorporate tried epidemiological methods to minimalize bias and confounding and to optimize statistical power. Microbiome data typically are highly variable, not only between persons but also within one person over time, and one must take that into account when designing studies. I therefore call on microbiome researchers to turn the tide. All the low-hanging fruit has been picked."

For the full text of Janneke van de Wijgert's inaugural lecture, click here

About Janneke van de Wijgert

Janneke studied medical biology and medicine at Utrecht University. She received her PhD in epidemiology from the University of California, Berkeley, USA. Janneke has extensive international experience in infectious disease-related clinical epidemiology research, public health research, product development and laboratory research. Janneke began her career in Zimbabwe, through the University of California, first as a PhD candidate and later as program director of an HIV research program. She then became director of a research program at the Population Council in New York. The main objective of this program was the development of HIV prevention tools for women. She returned to the Netherlands in 2003 to continue her international infectious disease research at Amsterdam UMC. In 2012 she became a professor at the Institute of Infection and Global Health at the University of Liverpool and in 2018 at the Julius Center for Health Sciences and Primary Care at UMC Utrecht. Janneke enjoys working in multidisciplinary teams where she builds bridges between disciplines. She supervises several PhD candidates and other students, is a sought-after advisor, speaker and peer-reviewer and has published 200 scientific articles.