The Official Blog of the Annual Translational Microbiome Conference

The official blog of the Annual Translational Microbiome Conference provides readers with information, insight and analysis regarding the microbiome.

New Tools are Needed to Drive Microbiome Research to the Next Level

These microbiome insights are brought to you by Dr. Peter Christey of GALT, Inc., and Arrowhead Publishers. Dr. Christey will be presenting "Driving the Tidal Wave of Microbiome Discovery - a Next Generation Platform for Exploring the Microbiome" at Arrowhead's 4th Annual Translational Microbiome Conference, 18th-20th April, 2018.

I so much enjoy microbiome meetings and continue to be blown away by the speed at which the field is developing and the innovative work being presented. However, there is a sense of frustration with many of the presentations and publications we see in the literature. You would have seen them - studies where samples are taken from healthy patients, samples are taken from diseased patients, next generation sequencing of the microbiome is performed and the results are compared. We get shown lots of charts showing that population x goes up, population y goes down. Then of course PCoA and other statistical charts are presented to demonstrate some point or other. All during the presentation I'm waiting for the punch-line, the insight that helps me understand what is going on. What is the microbiome doing? Who are the key actors? How are they impacting the disease state? What is the underlying biology, chemistry here? Data and insights that quench my curiosity. But no, the presentation ends once the sequencing data analysis is complete - we are left with that empty feeling that something is going on, but it is beyond our ability to understand.

Sequencing is an incredibly powerful tool that has helped illuminate the wonderful complexity and richness of the microbiome. It's one of the few, if not the only, research tools we currently have that scales to the complexity of the microbial systems we are studying. But is it enough? I feel we are doing the equivalent of trying to cure cancer solely by sequencing a million tumor samples. Cancer is being defeated by insights derived from multiple avenues of investigation, including clinical trials, epidemiological data, analysis of the underlying genetics and, critically, wet lab work dissecting the core biological mechanisms and pathways. Wet lab work is critical to test hypotheses and new ideas under controlled conditions - the path to getting from correlation to mechanism. Then we can seriously develop informed interventions to improve the human condition.

Microbiome wet lab work is constrained by the current toolset. Mainstream microbiology technologies were invented over 100 years ago. Core tasks, such as isolating target microbes, creating comprehensive strain collections or studying model ecosystems, are often difficult or impractical. We need new tools to drive microbiome research to the next level.

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YUN Overcomes European Regulatory Issues Surrounding the Use of Live Probiotic Bacteria for Topical Skin Application

These microbiome insights are brought to you by Dr. Ingmar Claes, Chief Scientific Officer at YUN, and Arrowhead Publishers and Conferences. Dr Claes will be presenting YUN’s work at Arrowhead’s 4th Annual Translational Microbiome Conference, 18th-20th April 2018. (www.microbiomeconference.com).

We all know that the skin is critical for our health by serving as a protective layer against external factors, but we tend to overlook the importance of the skin microbiome. The skin microbiome, acid mantle and epidermal skin barrier functions as our first layer of defense against pathogens. Use of products with live beneficial bacteria, also known as probiotics, pharmabiotics, or live biotherapeutic products (LBPs), have the potential of improving dysbosis for a multitude of skin disorders. Such restoration of the microbiome using ‘live’ probiotic bacteria to treat disorders is known as probiotherapy.

YUN is a Belgian-based biotech company with a totally new vision on health and hygiene. YUN aims to take healthcare to the next level. YUN believes in maintaining and restoring the skin microbiome; and the importance of the microbiome for human health. Working closely with leading probiotherapy experts from the University of Antwerp over the past decade, YUN has developed a world premier range of skin products including treatments for pimples (ACN and ACN+) and athlete’s foot (FNG).

World Premier ACN and ACN+ Products
YUN’s ACN and ACN+ products are the first creams (oil in water cream) in the world that contain ‘live’ probiotic bacteria in a dose that will have an impact on the skin microbiome. This major breakthrough was made possible by the development of an innovative type of microcapsule. This new microcapsule contains the ‘live’ bacteria in a core suspension, surrounded by multiple layers to protect them from the water in the cream. Furthermore, YUN strains are ‘probiotic’ which are specifically selected lactobacilli strains. These have some shared mechanisms of action with other probiotic strains, but also have some very specific properties against a selection of pathogenic or problem-causing micro-organisms such as Propionibacteriuim acnes, Trichiphyton spp, Staphylococcus spp., Malassezia spp., Candida spp.

Tough Regulatory Approval Challenges
LBP products face tough regulatory hurdles. Unlike the US in which the FDA’s Center for Biologics Evaluation and Research (CBER) has issued LBP guidelines for industry, the EU lacks regulatory framework. Regulations are lagging behind the new innovations. As in all regulations, safety is considered the most important factor. Thus, safety should always be the first concern when using LBPs.

As a completely new field of products for topical application, YUN faced tough European regulatory approval challenges. YUN has been looking from the start to market its products outside the EU, and it is clear that there are differences in regulations between the US and Europe. Indeed, regarding the FDA LPB product guidelines, it is unclear whether YUN’s topical products fall under the FDA’s definition of LBPs.

Further complicating matters is there are major differences between the safety assessment of oral medical drugs and LBPs for topical use. Specifically, for topical application, the challenges regarding safety should not be neglected. Even though our epidermal skin barrier, the acid mantle layer and the skin microbiome seem to be protective for systemic problems, carefully selected safe ‘probiotic’ strains should be selected for topical application.

As YUN’s topical skin care LBP products are safe and work by restoring or maintaining the skin’s natural defense layer, namely the skin microbiome, they fall in the EU under the cosmetic regulations. These products must not cause damage to human health when applied under normal or reasonably foreseeable conditions of use (cfr. Regulation (EC) N° 1223/2009) and data proving the safety of the probiotic strains being used must therefore be provided.
YUN specifically substantiated for the safety of all their topical products, both at the probiotic strain level and the final product itself. YUN goes even one step further as it wants to address the issues at hand of many of the current topical products which neglect safety on the skin microbiome.

Probiotic Strain Safety Research
YUN specifically performed research for the safety of the probiotic strains both in vitro and in vivo. Indeed, Dr Claes emphasized the importance of the safety of YUN’s probiotic strains particularly during the pre-clinical in vitro screening phase of development. Consequently, all the YUN’s strains were thoroughly characterized at the strain level. Mobile antibiotic resistance elements and virulence factors were investigated and excluded. Furthermore, interactions with human cells were also investigated.

Final Product Level Safety Research
At the final product level, aseptic filling, absence of contaminant pathogenic bacteria and amount of ‘live’ probiotic bacteria had to be proven by YUN. Additionally, the products with ’live’ probiotic strains were clinically evaluated by YUN to underline their level of safety for topical application on the skin.

Quality Control Issues
YUN guarantees the viability of its probiotic bacteria through patented breakthroughs in new galenic formulation and the development of microcapsules shielding its ‘live’ probiotics from water present in creams. Keeping the bacteria in a water-free core suspension ensures a minimal viable dose for up to six months at room temperature as the bacteria’s metabolical activity is minimal in the water-free suspension.

New Regulatory Framework is Needed
Dr Claes explains that by constructing the safety documentation and quality controls in the production of YUN’s products, they could be notified to EU authorities and placed safely on the market. It is therefore clear that safety is the most important aspect for LBPs and should always be addressed correctly. The added therapeutic benefits of these products for topical skin application might be the future for addressing specific skin disorders by using carefully selected probiotic strains.

Furthermore, YUN is a member of the Pharmabiotic Research Institute (PRI) and hopes to constructively interact with the European Medicine Agency (EMA). YUN believes that for some specific applications and products a completely new regulatory framework should be proposed for these new innovative products, which in the first place should always tackle safety before efficacy.

Clearly, approval regulation is lagging behind innovation. European drug authorities must tackle regulatory challenges to produce concise guidelines for industry in the development of LBPs. YUN deserves much credit for not only developing the world’s first ‘live’ probiotic creams in a dose to maintain and restore the skin microbiome, but overcoming tough European regulatory approval challenges.

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