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Topical Prebiotics for a Balanced Skin Microbiome. Is There Scientific Evidence?

Dr. David Caballero-Lima. R&D Manager. Labskin

Prebiotics and probiotics effect on human health and disease is a current issue that has aroused much interest in the scientific and industrial community.

The development of Next Generation Sequencing (NGS) which allows, among other exciting things, the study of the entire microbial community (the microbiome) of any given place has provided an additional way to investigate how prebiotics and probiotics work. We are just starting to understand the effect of pro/prebiotics on both the gut and our overall health.  New and exciting research has validated the gut-brain-skin axis hypothesis: a concept that suggests the importance of the gut microbiome on modulating stress-induced skin inflammation and the skin homeostasis.

However, less research has been focused in the study of topical prebiotics. This article will try to shed some light on the topic considering the available literature and our experience at Labskin.

Probiotic Lactobacilli Bacteria

We should start, then, by defining what probiotics and prebiotics are. Probiotics are microorganisms which live as part of the commensal microbiota of our body and are considered to be beneficial to us. Well known examples of those are gut bacteria such as Lactobacilli and Bifidobacteria. These microorganisms dwell inside our intestines fermenting nutrients that in most of the cases the human body is not able to digest. While doing so, they produce additional nutrients beneficial for our health, protect us against pathogenic microbes and regulate our natural defenses, i.e. the immune system.

We also have prebiotics, which are intrinsically linked to probiotics since they are nutrients, non-digestible by humans, which allow the beneficial bacteria that populate our organism to thrive while not enhancing the growth of pathogenic microbes. In a simple analogy, probiotics will be the machine while prebiotics may be considered the ghost in the machine. Natural compounds present in our diet, such as α-Oligoglucans, Inulin type fructans and β-Galacto-oligosaccharides have demonstrated specific prebiotic effects on beneficial bacterial groups in the gut such as Bifidobacteria, Lactobacilli and Bacteroides. The specificity of these compounds is due to the ability of these groups of bacteria to digest sugars and obtain energy from them.

Enzymes codified in their genomes break down the oligosaccharides allowing the microbes to feed on this energy source, which confer an advantage against other gut dwellers that do not contain such enzymes. Microorganisms that are able to digest Inulin and other fructans possess enzymes called β-fructofuranosidases (or fructanases), to digest β-Galacto-oligosaccharides they will have β-Galactosidases and to feed on α-Oligoglucans; α-glucosidases (α-amylases) that are able to break  down the α1🡪6 bond between glucans. All this occurs in the very specific environment of the bowel, an environment, which although variable and extensive has at least some well-defined characteristics: its pH tends to neutrality, it is rich in nutrients, it has high water content and it is mainly an anaerobic niche.

Skin could be considered a desert when compared to the gut.

In contrast, the skin could be considered a desert when compared to the gut. The environment on the human skin is much drier, less rich and in general more acidic (pH between 4-4.5) than the gut. Additionally, the skin environment could be considered as mainly aerobic. More environmental complexity can be actually found on the skin since it is the human body’s largest organ and as such very distinct niches can be identified.

In general terms, three main different environmental conditions can be found in human skin. A dry environment represented by arms and hands; wet environments that can be found in axilla, inguinal crease, umbilicus and feet and an oily environment represented, among other sites, by the back and face. All three can be considered fairly aerobic, however pockets of anaerobiosis will be available in all of them, mainly in the interior of sebaceous glands and hair follicles.

Nevertheless, the amount of nutrients and water available to microbial communities to thrive is greatly reduced when compared to the gut environment and it does not contain a source of oligosaccharides like the one provided by the diet. Thus, it is hardly surprising that the most common groups of bacteria found on human skin: Staphylococci, Corynebacteria and Cutibacteria; do not have the genes that codify for the enzymes necessary to digest those prebiotics. Evolution and natural selection have done their job. Searches in several gene and protein databases return no fructanases or β-Galactosidase present in those three groups of microbes. The three of them seems to have α-amylases (α 1🡪4) but only Cutibacterium acnes has a gene which codifies for an α-amylase (α1🡪6). However, in our experience, C. acnes is not able to grow with α-Oligoglucans as its only source of carbon.

Could oligosaccharides be used as topical prebiotics?

The question that arises, then, is: could oligosaccharides be used as topical prebiotics? They do not seem to have a prebiotic effect in the best-known beneficial commensal on human skin: Staphylococcus epidermidis. Oligosaccharides do not enhance the growth of the other main dwellers of the skin. I do not have the space here to discuss whether all Corynebacteria and Cutibacteria should be considered beneficial or detrimental, but it is worth noting that there is a large amount of evidence that C. acnes pathogenicity resides at the strain level.

Recent studies have, nonetheless, shown that the skin of people suffering from Atopic Dermatitis and Psoriasis presents a reduced number of Lactobacilli in general, and in particular of Lactobacillus iners. Would oligosaccharides be beneficial to alleviate these skin conditions? It is a possibility that will have to be further investigated.

What about essential oils like Cannabidiol, camphor, thymol and carvacrol?

What are the alternatives? Are there any? Thinking from an ecological and evolutionary perspective, which nutrients present in the skin might work as prebiotics? Which natural compounds from other sources will mimic that prebiotic effect? Some formulations in the market offer prebiotics based on lipids such as squalene, a naturally occurring lipid produced by sebaceous glands. However, some research points toward the involvement of squalene peroxidation on triggering inflammation on Acne vulgaris. Oat proteins have also been added to formulations with prebiotics claims but very little evidence supports those claims.

What about essential oils? A large number of essential oils used in cosmetics have been shown to have antimicrobial effect in a range of microorganisms belonging to distant groups.  Cannabidiol, camphor, thymol and carvacrol; all chemical compounds found in essential oils from plants display antibacterial effects against both Gram+  and Gram- bacteria. Therefore, at least some essential oils will not work as prebiotics.

In summary, there are some avenues being explored in the field of topical prebiotics. However, our knowledge is still very limited. More research will be  needed before prebiotic claims can be supported with evidence. Reproducible models to investigate the microbiome/host interactions at the skin site, such as Labskin, will be essential for this task.