Every person is different – just like every region of the body. On your scalp, in your mouth and under your arms live certain collections of microorganisms – in their ­entirety they are known as microbiomes. In order to use these microbiomes in product development, like for antidandruff shampoo, mouthwash and deodorants, Symrise has been expanding its research into this area for years. 

INNOVATION AND DEVELOPMENT

At the start of the study, lab assistant Jessica Grieger has a task that seems – to put it mildly – unusual for the layperson. Every morning she takes saliva samples from a broad range of Symrise employees, which they collect at home in small tubes. Only after this is done can the volunteer donors brush their teeth. In the lab for microbiology in Holzminden, Grieger mixes the samples and puts the liquid into 96 small reaction vessels that are arranged on a see-through plastic platter. A platter with 96 fake white teeth coated with hydroxylapatite, a natural component, is put on top as a lid.

The saliva will be thrown out the next day. In the meantime, a biofilm has appeared on the teeth – a visible layer of mucus built by microorganisms. Grieger, who completed training as a bioengineer alongside her Bachelor of Science in molecular biology, draws a nutrient medium into a multi-channel pipette. She fills the vessels on a new plate carefully and precisely, but still quickly, with the substance. She then closes them again with the same lid so that the biofilm on the teeth can continue to be nourished.

After two days, the preparation is ready. The formerly white fake teeth have become slightly yellow and smell strongly of what we would call bad breath. That’s all part of the plan. “We have used the model to recreate the oral flora, which consists of many different microorganisms such as bacteria, viruses and fungi,” explains Christin Koch of the process, which will subsequently serve to analyze the effect of dif­ferent test substances and products on the bacteria in the biofilm. She holds a doctorate in microbiology and heads the laboratory, which has developed an innovative focus in recent years: The research and development of molecules that target what is known as the microbiome.

Christin Koch heads the laboratory in Holzminden that researches the microbiome. This research is allowing Symrise to break new ground in product development.

“We have used the model to recreate the oral flora, which consists of many different microorganisms such as bacteria, viruses and fungi.”

Christin Koch
Head of the lab for microbiology

Research close to people

“People have their own little ecosystems in many places of the body that can be very different from each other. Their complex and dynamic interplay forms the larger ecosystem of a person,” says the scientist, who also dealt with the microbiome in her doctoral thesis. In the field of personal care products, research has traditionally focused on how certain substances affect the body and human cells, in particular with the goal of killing certain bacteria. Christin Koch, on the other hand, concentrates increasingly on the equilibrium of the human microbiome.

Their composition changes depending on the region of the body. The scientist compares them to eco­systems on earth: “The oral cavity is like a coral reef, the scalp like a flower meadow, the armpit with sweat and moist skin like a lush forest, or the dry skin on the shins like a desert.”

For research, it is therefore important to develop products that are as precise as possible and that work not only in vitro, i.e., in the test tube, but also in real life – in vivo, as the scientists call it. The test plate with the little teeth and saliva – that is, the ex vivo biofilm model – is aimed at this approach, as are the welding models developed in-house by the company. “For this purpose, our external cooperation partner sends men to the sauna, where they collect their sweat, which we can in turn use in the experiments,” says Koch of the research’s closeness to human life.

Drops of water

70%
The human body consists of almost 70 % water …

Human cell

3 x 1013
… and of approximately 3 x 1013 human cells.

Bacteria

3.8 x 1013
The number of bacteria is even higher. An estimated 3.8 x 1013 microbial cells populate our body and form our microbiome.

Benefiting the microbiome

With the findings from microbiome research, products have either been newly or further developed. An example of this is Crinipan® PMC Green, which hampers the growth of the Malassezia fungus. This fungus grows on the scalp and can cause dandruff. To do this, it relies on naturally occurring fats that it cannot produce itself. The product, which is derived from renewable raw materials, makes use of a “trick,” as Koch calls it: “Malassezia breaks down fat molecules present on the scalp to feed. These enzymes also release our Crinipan® PMC Green antifungal caprylic acid – an antifungal agent.” So Malassezia decimates itself, keeping the microbiome in balance.

In the area of deodorants, Symrise has developed the microbiome-friendly material SymDeo® B125. It can, for example, replace triclosan, which has a strong antimicrobial effect and prevents the smell of sweat, but also kills beneficial bacteria. And for the benefit of balanced oral flora, the ex vivo biofilm model has helped to take products such as Optafresh® D and SymReboot™ OC/Optabiotics®24 from the lab to the market. The former fights selected bacteria that create bad breath and simultaneously reinforces the bacteria that positively affect the oral microbiome, while the latter supports gum health.

The fact that microbiome research is possible in its current form is primarily due to technical progress. Although the first technologies for the DNA sequencing of the microbiome were available in the early 1990s, they have only been widely usable for the past ten years for cost-related reasons. “Today, the labo­ratories where we send our samples can generate and evaluate huge amounts of data in a very short time,” explains Koch.

Today, the labora­tories where we send our samples can generate and evaluate huge amounts of data in a very short time.Christin Koch, Head of the lab for microbiology

International networking

Symrise has invested heavily in microbiome research in the last few years, which also runs over into other divisions. Denis Guyonnet of Diana Nova wants to demonstrate how polyphenols, found in fruit and vegetables, have a positive effect on the gut microbiome. The secondary plant substances come primarily from fruits rich in polyphenols (for example, cranberries), as well as from the sidestreams of fruit and vegetable processing, such as peels or pomace, explains the innovation manager. In this process, Symrise performs standardized extraction of the polyphenols from these different raw materials to produce a product with specific polyphenols, because the type of polyphenols differ greatly from one fruit to another.

However, Guyonnet doesn’t just rely on research from within the Group. His task is also to connect the scientists with external academic researchers. The project on polyphenols has been running since 2018 in cooperation with the Université Laval (INAF) in Québec, and other research initiatives have been launched with world-class European experts in microbiology, gastroenterology and polyphenols. “We are working in two directions: We want to find out what effect the polyphenols have on the pathogens, the bad bacteria, and we also want to explore how to stimulate good bacteria,” says Guyonnet.

Both groups of bacteria play a role in intestinal health according to the researchers that work closely with the development group and Koch. “In a raw state, polyphenols can’t be absorbed. However, the bacteria of the gut can split them into small molecules, bringing out their anti-inflammatory and antioxidant capabilities,” explains Guyonnet. They also work against pathogenic bacteria. He emphasizes that people’s microbiomes differ from one another and that the complex research requires further investigation. For this reason, the five-year program will soon be followed by clinical trials.

Together with the Swedish biotechnology company Probi, in which Symrise has invested, he is also looking into innovative new synbiotic products containing living microorganisms. “These living bacteria can then directly break down the polyphenols from the fruits and release the active ingredients,” says Guyonnet. He is also working on this alongside his colleagues in Holzminden. “We can profit from the expertise of the entire Group – this is very efficient because paths are short and we can all work to the same quality standards. We can also access the broad natural portfolio throughout the company, which gives us a lot of options.”