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Skin Microbiome and Skin Disease: The Example of Rosacea

Picardo, Mauro MD; Ottaviani, Monica PhD

Journal of Clinical Gastroenterology: November/December 2014 - Volume 48 - Issue - p S85–S86
doi: 10.1097/MCG.0000000000000241
PRESENTATIONS
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The imbalance and/or the perturbation of the microbial populations that colonize the skin and that contribute to its defense may represent one of the causes of the development of noninfectious skin diseases. Atopic dermatitis, psoriasis, acne, and rosacea can be listed among these kinds of pathologies. In particular, considering that microbes have been long addressed as having a role in rosacea, this common dermatosis can be an interesting model to evaluate the correlation between microbiome alterations and the occurrence of clinical manifestations. Different microorganisms have been suggested to have a role in rosacea, but no direct correlation with the incidence of the pathology has been clearly defined. Skin microbiome composition is crucial for the correct skin immune functions and recent findings indicate an abnormal activation of innate immune system associated with the rosacea. The enhanced expression of toll-like receptor 2 in the epidermis of rosacea patients can represent a possible explanation for the amplified inflammatory response to external stimuli observed during the disease. In addition, significantly higher small intestinal bacterial overgrowth prevalence in rosacea subjects has been found and its eradication has been associated with a regression of the skin lesions. In conclusion, both skin and gut microbiome seem to have a role, even if synergistic with other factors, in the pathogenesis of rosacea. A deeper knowledge of human microbiome composition and microbe-host interactions will contribute to clarify the mechanism of development of rosacea and possibly will provide innovative therapeutic approaches.

Laboratory of Cutaneous Physiopathology, San Gallicano Dermatologic Institute (IRCCS), Rome, Italy

The authors declare that they have nothing to disclose.

Reprints: Mauro Picardo, MD, Laboratory of Cutaneous Physiopathology, Institute of Dermatology San Gallicano (IRCCS), Via Elio Chianesi 53, Rome 00144, Italy (e-mail: picardo@ifo.it).

The skin is the human body’s largest organ and represents the first barrier to environmental exposure acting as physical barrier and protecting from the assault of foreign organisms or toxic substances. Moreover, the skin is also colonized by a complex microbial population that include bacteria, fungi, and viruses, most of which are harmless or in some cases even beneficial to their host. The complex microbial populations that colonize the human body form the human microbiome. The composition of these microbial communities depends on skin characteristics such as sebaceous gland concentration, moisture content, temperature, as well as host genetics and environmental factors. A complex relationship exists between host and micro-organisms and for this reason both the presence of pathogens and the imbalance and/or perturbation in the commensal ecosystem have been associated with skin disease.1,2 These complex microbial communities may contribute even in the development of noninfectious pathologies such as atopic dermatitis, psoriasis, acne, and rosacea. Rosacea in particular seems to represent an interesting model to evaluate the correlation between microbiome and skin disease.

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ROSACEA

Rosacea, one of the most common dermatoses affecting primarily adults of 30 to 60 years of age, is a chronic cutaneous disorder characterized by centrofacial persisting erythema, telangiectases, papules, pustules, and phymas. Four different subtypes of the disease have been recognized, that is, erythematotelangiectatic (ETR), papulopustular (PPR), phymatous, and ocular, distinguished on the basis of specific clinical manifestations and morphologic characteristics.3 The pathogenesis has not yet been clarified but several factors have been identified as triggering ones such as solar exposure, dietary agents, and drugs. Abnormalities of the cutaneous vascular and lymphatic system, dermal matrix degeneration, and in some cases abnormalities of the sebaceous gland have also been described as factors implicated in the pathophysiology.

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ROSACEA AND MICRORGANISMS

Microbes have long been addressed as having a role in rosacea but the association between specific microbial colonization and incidence of the disease showed contradictory results. No one among the micro-organisms such as Helicobacter pylori, Demodex folliculorum, Staphylococcus epidermidis, and Chlamydia pneumonia has been identified as having a real causative role in the disease. Probably the collection of microbes populating the skin, more than a single micro-organism population has to be considered. Microbiome composition is crucial for the correct skin immune functions and together with the physical barrier functions account for the capability of the skin to detect potential dangerous events such as trauma and infection. Toll-like receptors (TLRs) represent one of the mechanisms by which innate immune system trigger inflammation by the recognition of specific microbial products or products of host injury.4–6 Recent findings have shown that rosacea patients present abnormal activation of innate immune pattern recognition receptors. The epidermis of subjects affected by rosacea express higher amount of TLR2 than healthy subjects indicating a possible explanation for the enhanced inflammatory responses to external stimuli. Moreover, enhanced expression of TLR2 can lead to abnormal production of cathelicidin antimicrobial peptides and increased expression and activity of serine protease kallikrein (KLK5), common characteristics of the disease. This finding suggest a role for the microbiome and TLR2 in controlling epidermal inflammation considering that in normal condition the collection of microbes populating the skin activate TLRs but do not promote inflammation.7

In addition, recent data indicate the potential pathogenetic role in the development of rosacea of small intestinal bacterial overgrowth (SIBO). Rosacea patients have a significantly higher SIBO prevalence than healthy subjects and its eradication leads to a significant regression of skin lesions. Moreover, rosacea patients SIBO-negative do not obtain any improvement after antibiotic therapy.8

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CONCLUSIONS

The role of micro-organisms in the development of rosacea as well as other skin diseases has not been clearly defined. The data available to date suggest that they may have a potential role, which seems to be rather synergistic with other factors, even though the real causative micro-organism has not been yet identified.

Recent metagenomic studies have uncovered a surprising diversity within microbiome and have indicated a much larger role in immune modulation and epithelial health than previously expected.

Defining the complexity of human microbiome and understanding microbe-host interactions and the factors driving microbial colonization could probably increase our knowledge about pathogenesis of different skin diseases and could help in the development of novel diagnostic tools and therapeutic treatments.

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REFERENCES

1. Chen YE, Tsao H. The skin microbiome: current perspectives and future challenges. J Am Acad Dermatol. 2013; 69:143–155.
2. Kong HH, Segre JA. Skin microbiome: looking back to move forward. J Invest Dermatol. 2012; 132:933–939.
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4. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003; 21:335–376.
5. Jiang D, Liang J, Fan J, et al.. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med. 2005; 11:1173–1179.
6. Taylor KR, Yamasaki K, Radek KA, et al.. Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J Biol Chem. 2007; 282:18265–18275.
7. Yamasaki K, Kanada K, Macleod DT, et al.. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol. 2011; 131:688–697.
8. Parodi A, Paolino S, Greco A, et al.. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008; 6:759–764.
Keywords:

rosacea; microbiome; skin disease; small intestinal bacterial overgrowth (SIBO)

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