The importance of skin microbiota in the development and testing of cosmetics and drugs

prof. Sebastian Granica, dr ha. Jakub Piwowarski
In April 2021, on the initiative of Jakub Piwowarski, MD, PhD, and Prof. Sebastian Granica, young scientists with over 10 years of experience in studying human intestinal microbiota, the environmental laboratory - Microbiota Lab - was established at the Medical University of Warsaw. One direction of research conducted by Microbiota Lab scientists concerns the interaction of xenobiotics (mostly natural compounds) with the human skin microbiota.

Human microbiota

Symbiotic bacteria, fungi and other microorganisms present in the human body together form what is called the human microbiome. Depending on the location of a particular microbial assemblage, there are different types of human microbiota, such as oral, vaginal, skin and intestinal microbiota. The latter two can be further grouped according to specific location, distinguishing, for example, microorganisms found behind the ear that may differ in composition and function from those living, for example, on the back of the hand or those found in different sections of the gastrointestinal tract. The composition and activity of the microbiota affects the host by regulating immune system function, conducting drug, food, and toxin metabolism, as well as forming a protective barrier against dangerous pathogens. Microorganisms found in the digestive tract may also be responsible for providing the host with essential nutrients and vitamins. In addition, numerous studies have shown an association between composition and function of microbiota with various diseases and disorders, such as irritable bowel syndrome, gingivitis, atopic dermatitis, colon cancer, non-alcoholic steatohepatitis, and mental illnesses.


Skin microbiota

The skin is the largest human organ and is responsible for many key human body functions such as thermoregulation and water-electrolyte balance. Recently, it has been shown that in addition to its basic tasks, the skin is the first protective barrier against all agents that can cause various diseases, by producing a complex and highly specialized system known as the SIS (skin immune system).

SIS contains not only the cells that make up the skin, such as keratinocytes, fibroblasts and lymphocytes, but also the microorganisms that live on the surface of the skin. Disruptions in the composition and function of the skin microbiota through the use of disinfectants, cosmetics or drugs can lead to the development of a variety of medical conditions.
The microbiota (mainly bacteria and fungi), on the other hand, may be responsible for the biotransformation (metabolism) of compounds in contact with it. This is especially true for the ingredients of cosmetics and drugs applied topically to the skin in the prevention and treatment of various diseases. A large group of substances applied to the skin are plant extracts and compounds of natural origin. Extracts obtained from such useful plants as Calendula officinalis and Symphytum officinale are included in many popular products available on the world market.
 

The influence of the microbiota on Metabolism

Previous scientific studies have shown that compounds introduced into the human body (xenobiotics) can be metabolized under the influence of bacteria found in various organs. Food and drug components taken orally are biotransformed by the microbiota in the gastrointestinal tract into new compounds that differ in chemical structure and properties from the original substances. The metabolism of xenobiotics by the gut microbiota is now fairly well documented. Research conducted by the Microbiota Lab team found that substances belonging to the group of tannins commonly found in foods such as fruits and nuts are converted in the colon to low-molecular-weight derivatives called urolithins. These compounds are then absorbed into the bloodstream and exhibit interesting biological properties. In contrast, the available literature lacks information on the metabolism of xenobiotics under the influence of other types of microbiota including skin microbiota.


Microbiota and atopic dermatitis (AD)

Today, one of the most prevalent and also a chronic condition in developed countries is atopic dermatitis (AD). Over the past decade, there have been numerous scientific studies linking the incidence of AD, in both adults and children, to skin microorganisms. The key interactions between microbiota and AD are explained by the so-called hygiene hypothesis. The hygiene hypothesis was developed on the basis of scientific research conducted in many centers around the world, which showed that good sanitation, limiting human contact with the surrounding bacteria from early childhood, causes the improper development of the body's immune response. The result is a depletion of the skin's microbiota causing a "dysregulation" of the immune system. Furthermore, having a balanced microbiota has been shown to play a key role in protecting against the onset of allergic diseases in both children and adults. The skin, which is home to countless bacteria, is colonized by different types of microorganisms, including those defined as symbiotic. One type of microorganism that plays this role is staphylococci, including cutaneous staphylococcus. These bacteria have been shown to produce specific substances with antibiotic properties that reduce the risk of pathogen infection by inhibiting their growth. A reduction in the population of cutaneous staphylococcus, which maintains the extremely delicate balance of the skin's microenvironment, may be one cause of the development of AD. A key role in disrupting the well-being of the skin microbiota is the use of cosmetics, detergents, disinfectants, and medications, whose ingredients often negatively affect bacterial growth.


MUW microbiota research laboratory - Microbiota Lab

In April 2021, on the initiative of Jakub Piwowarski, MD, PhD, and Prof. Sebastian Granica, young scientists with over 10 years of experience in studying human intestinal microbiota, the environmental laboratory - Microbiota Lab - was established at the Medical University of Warsaw. One direction of research conducted by Microbiota Lab scientists concerns the interaction of xenobiotics (mostly natural compounds) with the human skin microbiota.

In the Microbiota Lab, as part of the awarded NCN Preludium BIS project, the scientists from the MUW started research on the interaction of plant extracts, found in marigold (Calendula officinalis) and resinacea (Symphytum officinale) with the human skin microbiota. The influence of the tested extracts on the composition of the skin microbiota of healthy volunteers and the possible metabolism of the compounds contained in them under the influence of skin microorganisms was taken into account. Results obtained using chromatographic techniques showed that incubation of plant extracts with skin microbiota leads to a change in their composition. Consequently, the newly formed compounds may have different biological properties from the initial substances present in the extracts. This research provides a new perspective on the design and mechanisms of action of drugs or cosmetics applied directly to the skin that come into contact with symbiotic organisms living on its surface.

In the next stages of the study, it is planned to evaluate the effect of calendula and rosemary extracts on the biodiversity of human skin microbiota using NGS (Next Generation Sequencing) techniques, which is a key parameter indicating the proper condition of the skin.

The Microbiota Lab, based on the research infrastructure of the Center for Preclinical Studies and the Department of Pharmacognosy and Molecular Basis of Phytotherapy of the Faculty of Pharmacy, is the first in Poland and Europe specialized research and development unit focused on metabolomics and genetics of intestinal microbiota, skin microbiota, and other organs in humans and animals. Constantly developed unique apparatus facilities combined with the know-how of scientists enable Microbiota Lab to conduct complex research on microorganisms inhabiting different niches of the organism, compounds produced by them, and on metabolic products of drugs, toxins or food produced under their influence.