First proof for epidermal differentiation is directly influenced by S. epidermidis abundance on the skin surface
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Presented by: Leslie Landemaine
The role of bacterial gut microbiota has been extensively investigated in the last decade, and now more and more studies describe microbiota of other niches. Thus, the bacterial skin microbiota has been recently precisely characterized1. Its influence on skin health and skin development is likely but not yet clearly proven and deciphered. Elucidating the effect of skin commensals directly on skin is now a key path to better understand the role of the skin microbiota in skin health and disease.
Staphylococcus epidermidis is a coagulase negative commensal bacterium is generally considered as a key member of healthy skin microbiota, involved in the defense against pathogens2, modulation of the immune system and wound repair3.
Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis4, causing skin barrier damages and inflammation5
Recently, human skin equivalents models have been used as powerful tool showing pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community or a microbe at a single concentration6.
Thus, to better understand the effect of S. epidermidis on the skin we used reconstructed human skin model inoculated either with a low (103 UFC/cm²) or a high (106 UFC/cm²) load of S. epidermidis ATCC 12228 mimicking a healthy and disease states respectively and study their impact on epidermal differentiation by transcriptomic, histological analyses and measurement of cytokines secretion levels during 7 days of colonization.
We showed that the overabundance of S. epidermidis on the skin surface, significantly reduces the living epidermis thickness, modulates up to 1500 genes: mainly implicated in inflammatory response, and alters the differentiation of the epidermis at the gene expression and protein levels. Conversely, a low inoculum of bacteria does not affect the epidermis structure, nor inflammation and the epidermal differentiation complex genes (EDC) are preserved compared to the controls suggesting an adaptation of the epidermis to the presence of the bacteria.
In conclusion, this study shows a first direct link between S. epidermidis abundance and epidermis structure, differentiation, and inflammation context. All together, these data allow us to develop a simple healthy colonized human skin model. Further in vitro studies will be needed including other microbial species of the skin microbiome and other strains originated from healthy and normal skin origin. However, this constitutes a major step in the understanding of the importance of the good balance of S. epidermidis quantity for healthy skin quality.
References:
1. Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nature rev. microbiol. 16, 143–155 (2018).
2. Nakatsuji, T. et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 9, (2017).
3. Linehan, J. L. et al. Non-classical immunity controls microbiota impact on skin immunity and tissue repair. Cell 172, 784-796.e18 (2018).
4. Byrd, A. L. et al. Staphylococcus aureus and S. epidermidis strain diversity underlying human atopic dermatitis. Sci. Transl. Med. 9, (2017).
5. Cau, L. et al. Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis. J. Allergy Clin. Immunol. (2020)
6. Loomis et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome (2021)
Staphylococcus epidermidis is a coagulase negative commensal bacterium is generally considered as a key member of healthy skin microbiota, involved in the defense against pathogens2, modulation of the immune system and wound repair3.
Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis4, causing skin barrier damages and inflammation5
Recently, human skin equivalents models have been used as powerful tool showing pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community or a microbe at a single concentration6.
Thus, to better understand the effect of S. epidermidis on the skin we used reconstructed human skin model inoculated either with a low (103 UFC/cm²) or a high (106 UFC/cm²) load of S. epidermidis ATCC 12228 mimicking a healthy and disease states respectively and study their impact on epidermal differentiation by transcriptomic, histological analyses and measurement of cytokines secretion levels during 7 days of colonization.
We showed that the overabundance of S. epidermidis on the skin surface, significantly reduces the living epidermis thickness, modulates up to 1500 genes: mainly implicated in inflammatory response, and alters the differentiation of the epidermis at the gene expression and protein levels. Conversely, a low inoculum of bacteria does not affect the epidermis structure, nor inflammation and the epidermal differentiation complex genes (EDC) are preserved compared to the controls suggesting an adaptation of the epidermis to the presence of the bacteria.
In conclusion, this study shows a first direct link between S. epidermidis abundance and epidermis structure, differentiation, and inflammation context. All together, these data allow us to develop a simple healthy colonized human skin model. Further in vitro studies will be needed including other microbial species of the skin microbiome and other strains originated from healthy and normal skin origin. However, this constitutes a major step in the understanding of the importance of the good balance of S. epidermidis quantity for healthy skin quality.
References:
1. Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nature rev. microbiol. 16, 143–155 (2018).
2. Nakatsuji, T. et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 9, (2017).
3. Linehan, J. L. et al. Non-classical immunity controls microbiota impact on skin immunity and tissue repair. Cell 172, 784-796.e18 (2018).
4. Byrd, A. L. et al. Staphylococcus aureus and S. epidermidis strain diversity underlying human atopic dermatitis. Sci. Transl. Med. 9, (2017).
5. Cau, L. et al. Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis. J. Allergy Clin. Immunol. (2020)
6. Loomis et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome (2021)