Science Nature Beauty

40 years of expertise in microbiome research – Interview with Dr. Heiko Prade, Director R&D at CLR

Dr. Heiko Prade is Director Research & Development at CLR.
In our interview he talks about the history of CLR’s microbiome expertise, shares insights on the current state of skin microbiome research and gives an outlook on future developments in the field.

Dr. Prade, please tell us about the history of research on probiotic bacteria at CLR.

Not long ago, the concept of ‘probiotics’ became a big trend in the cosmetics industry. We already had been working with probiotic bacteria for the development for our active ingredients for decades, but, as a company, we have always been strongly focused on science and much less on marketing. We are very happy to see that this is now a trend, but, above all, we see this as a very important technology. It needs to be said, though, that, as with all technologies, biotechnology can only be important, when used in the right way.

Over the last 40+ years, we have found that probiotic bacteria can be a very good source for the development of potent and safe active ingredients for the cosmetics industry, but only when we understand both the bacteria and the effects of the processing parameters we expose them too. We have learnt that the quality of the active ingredient relies strongly on the fermentation process itself, but also on the downstream-process. The way we lyse bacteria and the applied filtration technology have a strong impact on the activity. The species of bacteria plays an important role in the activity too, but the processing is even more important.

We have also learnt a lot about the mechanistic aspects of the interaction between molecules which are produced by the bacteria and human cells. This knowledge is tremendously important for us to develop our products in the best and most efficient way.

Not just probiotic bacteria, but unicellular microorganisms in general, are a source for active ingredients with high potency and safety. Biotechnology has evolved strongly over the last 40 years, which helps and will continue to help us in developing active ingredients which work extremely well, not just from a scientific point-of-view, but also in the perception of the consumer.


How much time and effort does it take to develop an active ingredient based on probiotic technology?

The development process can take quite long. For instance, the development of our Bifida Ferment Lysate began in the mid-1970’s. At that time, we started a co-operation with the Free University of Berlin, in particular with Dr. Martin Kludas. Dr. Kludas was one of the pioneers in Europe when it comes to the science behind probiotic bacteria and their interaction with the human body. Interestingly, already in 1960, Dr. Kludas had published about the role of the gut bacteria in dermatoses. Already then, he had a large focus on probiotic bacteria and their outcome for the skin. Together with Dr. Kludas, CLR came up with the idea of developing an active ingredient for the use in cosmetic skincare products.

The rationale behind this thinking was that the beneficial interaction between ‘good bacteria’ and human cells was largely based on biochemistry, where bacterial molecules interacted with human cells through, for instance, cellular receptors.

A lysate of a beneficial probiotic bacterial species could suffice to obtain strong effects for the human skin. As the interaction between microbes and our body was already understood to give immunological benefits to our body, another co-operation was initiated. Together with Dr. Kludas, CLR started to work together with the university of Freiburg, in the southwest of Germany. In this co-operation, a close look was given on the anti-immunosuppressive effects of the Bifida Ferment Lysate which had been developed. UV-radiation from the sun has an important detrimental effect on the skin. It damages skin and skin cells, but it is also immunosuppressive, which means that the ability to react to the damage caused, is reduced. Immunosuppression plays an important role in skin aging and with our Bifida Ferment Lysate it was shown that it could strengthen the immunocompetence of skin cells, essentially counteracting UV-induced immunosuppression. With that, Bifida Ferment Lysate was shown to be an important active ingredient which helps slowing down the skin aging process.

In 1982 our Repair Complex CLR™ (INCI: Bifida Ferment Lysate) was launched and, since then, has been used in many different cosmetic formulations.


In the field of skin microecology, what are the latest research results and research directions of CLR?

We indeed see the skin as an ecosystem. The Baas-Becking hypothesis (“Everything is everywhere, but the environment selects”) is a key-philosophy for us. The skin and the outside world provide an environment for our healthy resident skin microflora to flourish in. Microbes for which the environment of the skin is detrimental, might try to colonize the skin, but will not be able to do so sustainably. These microbes are part of our transient skin microflora.

Another important realization for us is that epidermal skin microflora cannot just be found on the surface of the skin, but also in the deeper layers of the upper stratum corneum, the stratum disjunctum. In the deeper stratum disjunctum the epidermal skin microflora multiplies and flourishes. Here, the microbes adhere to the epidermal corneocytes which are in the upward movement and, together with these dead skin cells, are shed from the skin after reaching the surface. At the same time, though, in the deeper stratum disjunctum, new microbes are formed constantly. In essence, like the epidermis itself, the skin microflora renews itself from the inside out. In this way, it is able to maintain its composition, despite that microbes are constantly stressed, killed or rubbed-off at the skin’s surface.

For us, healthy skin has a healthy skin microflora. Healthy skin shows an effective and fully functional epidermal differentiation process. With one of our products, ProRenew Complex CLR™ (INCI: Lactococcus Ferment Lysate), we were able to show that, through its potent action on the quality of the epidermal differentiation process, it was able to play an important supportive role for the skin microflora. It indeed improves the skin as an ecosystem.


What can we expect from skin microbiome research in the near future?

Science now allows for a description of the composition of the human microflora. Although there are still many areas where the technologies which are important for this can be improved, we can already come to quite strong conclusions on which microbes live in which areas of our body.

Future research needs to have a focus on gaining detailed information about the interaction between the microbial and human cells. In a healthy situation, this interaction looks to be strongly symbiotic, where both profit from each other. There is still very little known about the mechanisms of this interaction, though. This knowledge will help us in gaining more detailed understanding of both the beneficial role of our skin microflora, as well as which role they play in important cosmetic features of our skin, like sensitivity and aging. At CLR we perform our own research and we are closely following the results of the leading international research groups in this particular field.

Worldwide, basic research on the skin microflora has been largely focused on diseased skin. Lots of knowledge has been gained on the microflora’s role in atopic and seborrheic dermatitis, psoriasis, rosacea or acne, for instance. Academia’s focus on treating diseases is understandable, but not necessarily of large importance for the cosmetics industry. Cosmetic skincare products, by definition, are not allowed to treat a disease, they are only allowed to better protect our skin or to provide care.

In our opinion, there should be a larger focus on the skin microflora’s role on the health of skin. Looking on pathogenic skin conditions helps gaining valuable knowledge since, admittedly, performing research on ‘health’ is far more complicated than performing research on ‘disease’.


What are the directions for the innovation of active ingredients supporting the skin microbiome?

With the current lack of knowledge about the exact positive or, in the cosmetic context, detrimental mechanistic nature of the microbial-human interaction, at CLR, we are of the opinion that it is not possible to define which microbes are essentially ‘good’ or ‘bad’ for our skin. A well-known example is Cutibacterium acnes. C. acnes was always seen as the ‘acne-bacterium,’ which we aimed to kill to obtain anti-acne effects. Just recently it became clear that only certain phylotypes of C. acnes play a role in acne, whereas other phylotypes help our skin in the defense against pathogens. Another good example is Staphylococcus epidermidis, which many people consider to be solely ‘good’. This species can play a negative role on our skin too.

Consequentially, we are focused on the skin microflora as a whole and do not aim to support the growth of single species which we might expect to be ‘good’, but might well be not all that good. Therefore, prebiotics or any other active ingredients, which do not support the skin microflora on healthy skin as a whole, but which only support the growth of certain species, in our view, do not strictly make sense when it comes to create products for healthy skin

With our active ingredients, our philosophy has always largely been, ‘to help the skin to help itself’. Through our research, we have now learnt that by helping the skin, we are also helping its microflora, especially the epidermal microflora. To us, the skin comes first, in the sense that the skin provides the environment for the skin microflora. If the skin is healthy and the epidermal differentiation processes take place optimally, the epidermal microflora is healthy.

Future research will focus on defining the exact nature of the role of the skin in cosmetic features where the skin microflora is also implied. For example, what roles does skin play in the changes in the composition of the skin microflora during aging and what implications does the change in microbial composition of the skin play in skin aging? Human-microbial interaction is intensive and it is a ‘two-way street’ where a positive feedback loop can change into a vicious circle where both negatively influence each other.

Looking on new anti-virulence strategies that fit into a cosmetic approach is also within our scope. Many microbes can change from good to bad guys when they start producing certain virulence factors (e.g. biofilm formation), which often is a typical response to environmental stress.


Regarding microbiome skin care products, what are the main difficulties and challenges currently faced?

Cosmetics industry is facing different challenges. There are still many scientific challenges, as described above, and clearly more thorough understanding is needed. Other important challenges are consumer understanding and lie within the cosmetics industry itself, though.

Far better than in the past, the consumer understands that our body largely depends on our microflora for health. This is thanks to the food industry and their products containing probiotic bacteria.

It is up to the cosmetic industry to educate the consumer and gain further interest. This is where another important challenge lies. It is a worldwide phenomenon that trust in the cosmetic industry is low. Consumers tend to not believe what the cosmetics industry tells them. In our view, this is the biggest challenge the cosmetics industry is faced with. These days consumers are clearly more knowledgeable and critical about the cosmetic products they use than in the past. In general, they want the cosmetics industry to provide them with safe and efficacious products, without making promises which cannot be kept. It is interesting to see that brands which have an approach where they tend to be honest to consumers, are successful. We think that such an approach is needed for the consumer to become well educated about the skin microflora. The skin microflora is far too important for our skin to just make it a marketing trend.



Dr. Heiko Prade

Director Research & Development