From pattern to patient: microbiome research needs to bridge the gap to the clinic

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The microbiome has been a trending scientific topic in recent years. Researchers have uncovered correlations between the human microbiome and a wide range of diseases and health states, ranging from digestive issues to mental wellbeing. But no matter how fascinating these academic findings may be, translating them into concrete clinical applications remains a challenge. How can we enable more efficient clinical valorization of microbiome insights, and pave the way from pattern to patient?

The microbiome: a deep well of possibilities

“We are not alone” is potentially the most popular catch phrase referring to the trillions of micro-organisms we carry along with us. This microbiome has been the subject of numerous sampling initiatives and research projects over the past few decades. Starting in the early 2000s with culture-based techniques, the revolution in (meta-)genomics and bioinformatics has since transformed the field, uncovering the microbiome’s potential in diagnosing, predicting, and treating disease. Initial focus on the intestinal flora has expanded to other niches, including the skin, reproductive system, and virtually any other body part inhabited by microbes.

“Despite the enormous impact that microbiome developments could have on our health and wellbeing, translating these insights into optimized heath care is not a straightforward process – so far, adoption in clinical settings has been limited.”

About two decades on, we have compiled an immense amount of information about the human microbiome. We can use microbial compositions to predict not only the onset and type of disease, but even a particular patient’s likelihood of responding to treatments. By targeting the microbiome (e.g. using pre- and probiotics or fecal microbiota transplants), we can treat conditions, improve therapeutic responsiveness, and reduce the side-effects of other medications. Yet despite the enormous impact that microbiome developments could have on our health and wellbeing, translating these insights into optimized heath care is not a straightforward process – so far, adoption in clinical settings has been limited.

Overcoming gaps on the road towards clinical applications

The relative infancy of the field, and the complex nature of the data, are currently limiting the integration of microbiome-based therapies in clinical care. Most microbiome studies today are still observational, aiming at correlating microbial composition with a person’s state of health. In addition to being relatively scarce, trials assessing efficacy and safety of microbiome-based therapies are often statistically underpowered and suffer from variable outcomes. Microbiome-based therapies are indeed seldom universally deployable because of the great deal of interpersonal variation in microbial composition. This does however open up the possibility of personalized care – a complex yet promising field in which patients receive health care specifically tailored to their precise needs. Coupled with the extreme pace at which the field is evolving, these factors make it difficult to integrate insights into uniform protocols and guidelines that are useful to healthcare professionals. Finally, a lack of awareness of the basic science and potential of microbiome-based therapies regularly leads to distrust among both clinicians and patients.

“Clinicians and scientists have to connect with each other.”

Although the road from lab to hospital seems long and bumpy, these obstacles can be overcome. Paving the way will however require additional support. Firstly, we need clearer communication towards patients and especially clinicians. Healthcare professionals have to be provided with training on best practices for microbiome-based procedures and interpretation of patient data. Laboratories will play an important role in providing services on fast analysis and support of data interpretation. We should make uniform guidelines for data analysis and processing available, and potentially even qualified through accreditation. Meanwhile, scientists need to improve their study designs, to make sure that they take the user and application into consideration (which currently isn’t happening often enough). In short, clinicians and scientists have to connect with each other. This connection could be facilitated through collaborative projects, conferences focused on translation, and other mutual initiatives.

Tackling fertility issues: an example of clinical collaboration in action

A microbiome-based approach may present a solution for fertility issues caused by endometritis. Chronic endometritis involves inflammation of the endometrium (the lining of the uterus) and is potentially caused by an imbalance between the local microbiome and the person’s immune system. Endometritis occurs in about 10% of women but, partially because symptoms can be mild to non-existent, it usually goes undetected. Unfortunately, fertility treatments seem negatively impacted when women suffer from endometritis. Nowadays, these women typically undergo several rounds of antibiotic treatment before starting their fertility process.

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Researchers are now trying to develop a targeted microbiome-based strategy to help resolve the issue. In a large-scale citizen science project called ISALA, Prof. Sarah Lebeer from UAntwerp collected over 4000 vaginal swabs from healthy Flemish women and mapped the microbiome. “As ISALA mapped the microbial composition of the healthy vagina, it can be used as reference and starting point for additional research diving into particular disease conditions,” says Lebeer.

At UZ Brussel, Prof. Shari Mackens and Dr. Thomas Demuyser’s team is building bridges between the fundamental research performed at the Lebeer lab and its application in the fertility center. Mackens is positive about the approach: “We have indications that targeting the microbiome has an impact on IVF success rates and try to understand how we can use this information in daily clinical practice.”

With their newly funded FLORA project, the team aims to identify the microbial cause of chronic endometritis, to lay the foundations for further research on facilitating successful pregnancies. The collaboration between research and clinic is essential to achieving results. “The FLORA project is an example of how researchers and clinicians come together to achieve a common goal,” Demuyser concludes. “Collaboration is not an option – it is absolutely vital to making a change.”