Lipotec reinforces urban skin by reconnecting with the origins

Urbanisation has reduced our interaction with nature, triggered the prevalence of inflammatory disorders and skin sensitivity. Lipotec’s new Fensebiome peptide helps strengthen vulnerable urban skin by promoting a healthy microbiome and reinforcing skin’s barrier function.

Discomfort, fragility, dehydration, scaliness and redness are all characteristics of sensitive skin. Its intolerance to external aggressors has increased in consumers in most urban areas. This evidence suggests reduced exposure to nature may be related to an increase in the risk of inflammatory skin conditions. Yet the skin of our ancestors, who were in closer contact with nature, was more resilient.

The discovery of an isolated Yanomami hunter gatherer village in the Amazon jungle, whose people did not have any previous contact to modern lifestyles, provided an opportunity for vital microbiome research. The research compared the Yanonami skin microbial genome to that of urban individuals, who had a reduced connection to nature and higher antimicrobial practices. Results suggested the exposure to modern lifestyles may induce alterations in the cutaneous microbiota, such as a reduction in bacterial diversity, which could make skin prone to sensitivity and discomfort.1

Skin’s double barrier

A vital function of the skin microbiota is to contribute to skin’s role as a protective barrier; this can occur through different mechanisms. Through direct competition for space and nutrients, beneficial bacteria can cause the exclusion of potentially harmful bacteria.2 The reciprocal interaction of microbiota with keratinocytes helps enhance the innate immune response, allowing pathogen recognition to prevent their invasion, while promoting maintenance.3, 4

The mechanical wall that resides on the epidermis is also crucial to provide an efficient permeability barrier against excessive loss of water and electrolytes. It also protects the organism from harmful elements of the environment. Among its main elements are the intercellular junctions – the tight junctions found in the stratum granulosum and the lipid barrier in the stratum corneum.

In particular, sensitive skin is characterised by an abnormal microbial colonisation, an impaired barrier function and an aberrant lipid organization.5

The new Fensebiome peptide (INCI: Aqua, Caprylyl Glycol, Acetyl heptapeptide-4) is a heptaptide, available in South Africa from Savannah Fine Chemicals. It is is intended to strengthen exposed urban skin by reinforcing barrier function and preventing dehydration. The efficacy of the active ingredient was evaluated through several in vivo and in vitro tests.

Favorable skin microbiome

A metagenomics analysis was performed on 21 female urban volunteers aged between 18 and 59. They applied a cream containing one percent Fensebiome peptide solution on the cubital fossa of one arm and a placebo cream on the other, twice a day. Several microbiome parameters were assessed after seven days of treatment.

The diversity of skin bacteria, which is higher in the skin of people living in close proximity to nature, was determined using the Shannon index – an indicator of skin health. After the active treatment, the Shannon index value showed a higher increment compared to the placebo, indicating increased bacterial diversity for a rewilding effect, which leads to better skin health.

The relative abundance was evaluated at the phylum and family taxonomic levels. At the end of the treatment, the active ingredient helped increase the relative abundance of the beneficial bacterial phylum of Proteobacteria by 15.2 percent (p<0.01). It also reduced the Firmicutes phylum by 21.3 percent (p<0.01), achieving a balanced microbiome for healthy skin.

At the family level, it helped increase the relative abundance of Moraxellaceae by 6.4 percent (p<0.01), which belongs to the gammaproteobacterial class, which demonstrates anti-inflammatory properties related to immunological homeostasis and has been found on the skin of people living in close proximity to nature. The ingredient also showed a reduction in Staphylococcaceae by 25.1 percent (p<0.001), which is mostly associated with skin conditions such as atopic dermatitis and psoriasis.

A predictive microbial functional profile was obtained and represented using KEGG pathway mapping. The peptide helped enhance bacterial metabolic pathways related to energy, lipids, amino acids, carbohydrates and vitamins. These elements have been detected in the skin of isolated populations and could promote the external supply of nutrients to the skin.

Enhanced skin cell cohesion

A panel of 18 female urban subjects aged between 26 and 50, who presented dry skin on the legs, applied a cream containing one percent Fensebiome peptide solution on one shin and a placebo on the other, twice a day for seven days. Samples of the stratum corneum were obtained by tape stripping and visualised using fluorescence.

Four fluorescence microscopy images obtained from different strips before and after each treatment

The active treatment decreased sloughed corneocytes by 18.6 percent (p<0.05), reducing scaliness.

Barrier protection effect

A group of 20 female urban volunteers aged between 22 and 45 applied a cream containing one percent Fensebiome peptide solution and a placebo cream on the forearm, twice a day for seven days. TEWL was evaluated after surfactant damage which the peptide helped decrease by 27.8 percent. These results suggest an improved protective effect on the physical barrier to prevent dehydration.

A graph showing how TEWL decrease versus damage after different treatments

Encourage adhesion of beneficial skin microbiota

Human keratinocytes were pre-incubated for 24 hours with 50μg/mL Fensebiome peptide or a culture medium as the control. The epidermal cells were exposed to a mixture of S. epidermidis labelled with green fluorescence and inactivated red-fluorescently labelled S. aureus. The adhesion of each type of bacteria to the keratinocytes was determined using fluorescence microscopy.

Fluorescence microscopy images showing Keratinocytes nuclei pre-incubated with either the medium or the active treatment and adhesion of S. epidermidis in green and S. aureus in red

The active treatment favoured the adhesion of S. epidermidis instead of the potentially pathogenic S. aureus in keratinocytes.

Immune response modulation

The expression profile of a set of genes related to the activation of immune response was obtained by means of a transcriptomics study.

Human keratinocytes were treated with 50μg/mL Fensebiome peptide for 24 hours, while cells treated with a culture medium were used as the control. Gene expression was assessed through an RT-PCR array.

Results showed an induction of different genes related to Toll-like receptors (TLRs) and nucleotide oligomerisation domain-like receptors (NLRs) signalling pathways that could help prepare skin’s cells to respond efficiently in protecting against a wide range of harmful microbes when needed.

Key epidermal barrier compartments reinforced

These tests aimed to study the peptide’s ability to increase gene expression linked to the improved functionality of the epidermal barrier and to evaluate the differences between the control and treated skin in terms of the presence of ceramides.

Human keratinocytes were treated with 50μg/mL Fensebiome peptide for 24 hours or with a culture medium as the control. An RT-PCR array was performed to assess the expression levels of genes related to tight junctions (TJs).

Reconstructed human epidermis models were also treated with 50μg/mL Fensebiome peptide for 24 hours or a culture medium as the control. Ceramides levels in the reconstructed human epidermis were evaluated by means of lipidomics.

The active ingredient helped increase the expression of components of the cell’s TJs, which provide impermeability to the barrier, preventing loss of water and solutes and reinforcing protection against pathogen invasion. In addition, the peptide helped boost the number of long-chain ceramides essential for the structure and impermeability of the barrier function.

Improved epidermal barrier functionality

Two different dye penetration assays, which can be used as in vitro indicators of TEWL, were performed.

Performance of the TJs in the granular layer of the epidermis was tested using biotin as a tracer molecule. Biotin can pass through intercellular spaces yet not through properly functioning TJs.

Reconstructed human epidermis models were incubated for 24 hours with 50μg/mL Fensebiome peptide and 0.02mg/mL sodium dodecyl sulfate (SDS). Skin models treated with a medium were used as the control and reconstructed human epidermis models incubated with 0.02mg/mL SDS and the medium were used as a positive control for barrier disruption. Then, a biotin tracer was added at the bottom of the epidermis models for 30 minutes to allow its inside-out diffusion. Presence of biotin tracer in the different layers was assessed by quantifying microscopy images.

Microscopy imaging showing inside-out diffusion through reconstructed human epidermis models. The presence of the tracer is observed in green with cell nuclei are stained in blue

Biotin penetration was inhibited by 64.8 percent (p<0.0001) compared to the positive control, suggesting a reinforced barrier that can resist damage induced by SDS.

The intercellular lipids were evaluated by measuring the outside-in diffusion of toluidine blue dye from the epidermal surface. Reconstructed human epidermis models were treated with 0.02mg/mL SDS, to induce a disruption of the stratum corneum in the presence or absence of 50μg/mL Fensebiome peptide. Models treated with a medium were used as the control. After 24 hours, the dye was added to the epidermis models for 10 minutes and its diffusion across the epidermis evaluated using microscopy imaging.

Microscopy imaging showing outside-in diffusion of the toluidine blue dye into the stratum corneum under different conditions

A decreased penetration of tracer dye was observed despite the presence of SDS, suggesting a strengthening of the barrier that prevents alterations by chemical aggressors.

Concluding results

Fensebiome peptide helps boost the defence system of skin exposed to harsh urban environments and sensitive skin types by favouring microbiota diversity and improving the skin immune response and physical barrier integrity.

A metagenomics analysis on volunteers exposed urban environments showed the active ingredient helped increase the skin microbial diversity. It also showed how it favoured the presence of beneficial bacteria and modulated bacterial metabolic pathways, which are all markers of the healthy and protected skin of people living in close proximity to nature.

Other clinical studies on urban volunteers showed Fensebiome peptide’s ability to reinforce cell cohesion and reduce TEWL levels after damage, suggesting a protective effect of the skin barrier.

In vitro tests showed the peptide it favoured the adhesion of beneficial bacteria over that of pathogenic bacteria on keratinocytes. It helped induce genes associated with the activation of immune response and tight junctions, with a key role in epidermal barrier integrity. The ingredient also favoured an increase in long-chain ceramides, essential for a well-preserved barrier function and it improved the resistance to aggression by surfactants.

References:

  1. Clemente J, et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1:e1500183, 2015.
  2. Chiller K, Selkin B, Murakawa G. Skin microflora and bacterial infections of the skin. Journal of Investigative Dermatology Symposium Proceedings. 6(3):170-174, 2001.
  3. Sanford J, Gallo. Microbial symbiosis with the innate immune defence system of the skin. J Invest Dermatol. 131(10): 1974–1980, 2011.
  4. Von Herzen L, Hanski I, Haahtela T. Natural immunity. EMBO reports. 12(11):1089-1093, 2011.
  5. Zaniboni MC, Samorano LP, Orfali RL, Aoki V. Skin barrier in atopic dermatitis: beyond filaggrin. An Bras Dermatol. 91(4):472-8, 2016.

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