Abstract
Background
The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea.
Objective
We performed a case–control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race.
Methods
Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software.
Results
Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%).
Conclusions
The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.
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References
Wilkin JK. Rosacea: pathophysiology and treatment. Arch Dermatol. 1994;130:359–62.
Powell FC. Clinical practice: rosacea. N Engl J Med. 2005;352(8):793–800.
Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46(4):584–7.
Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2004;50(6):907–12.
Powell FC. What’s going on in rosacea? J Eur Acad Dermatol Venereol. 2000;14:351–2.
Whitfeld M, Gunasingam N, Leow LJ, et al. Staphylococcus epidermidis: a possible role in the pustules of rosacea. J Am Acad Dermatol. 2011;64(1):49–52.
Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am Acad Dermatol. 1993;28(3):443–8.
Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol. 2007;157:474–81.
Murillo N, Mediannikov O, Aubert J, Raoult D. Bartonella quintana detection from Demodex in erythematotelangiectatic rosacea patients. Int J Infect Dis. 2014;29:176–7.
Kong HH. Skin microbiome: genomics-based insights into the diversity and role of skin microbes. Trends Mol Med. 2011;17(6):320–8.
Kong HH, Oh J, Deming C, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012;22:850–9.
Kong HH, Segre JA. Skin microbiome: looking back to move forward. J Investig Dermatol. 2012;132(302):933–9.
Gao Z, Tseng C, Strober BE, et al. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One. 2008;3(7):1–9.
Clauvand C, Jourdain R, Bar-Hen A, et al. Dandruff is associated with disequilibrium in the proportion of the major bacterial and fungal populations colonizing the scalp. PLoS One. 2013;8(3):1–8.
Roghman MC, Lydecker AD, Hittle L, et al. Comparison of the microbiota of older adults living in nursing homes and the community. mSphere. 2017;2(5):e00210–7.
Bromberg JS, Hittle L, Xiong Y, et al. Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes. JCI Insight. 2018;3(19):121045.
Fadrosh DW, Ma B, Gajer P, et al. An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform. Microbiome. 2014;2(1):6.
Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–6.
White JR, Nagarajan N, Pop M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol. 2009;5(4):e1000352.
Clarke KR. Non-parametric multivariate analyses of changes in community structure. Aust J Ecol. 1993;18(1):117–43.
The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2013;486(7402):207–14.
Chao A, Chiu CH, Jost L. Phylogenetic diversity measures and their decomposition: a framework based on Hill numbers. In: Pellens R, Grandcolas P, editors. Biodiversity conservation and phylogenetic systematics: topics in biodiversity and conservation, vol. 14. Cham: Springer; 2016.
Hamandy M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4(1):17–27.
Zaidi AK, Spaunhurst K, Sprockett D, Thomason Y, Mann MW, Fu P, et al. Characterization of the facial microbiome in twins discordant for rosacea. Exp Dermatol. 2018;27(3):295–8.
Murillo N, Aubert J, Raoult D. Microbiota of Demodex mites from rosacea patients and controls. Microb Pathog. 2014;71–72:37–40.
Leyden JJ, McGinley KJ, Mills OH, Kligman AM. Age-related changes in the resident bacterial flora of the human face. J Investig Dermatol. 1975;65(4):379–81.
Barnard E, Shi B, Kang D, et al. The balance of metagenomics elements shapes the skin microbiome in acne and health. Sci Rep. 2016;6:39491.
Marples RR, Downing DT, Kligman AM. Control of free fatty acids in human surface lipids by Corynebacterium acnes. J Investig Dermatol. 1971;56(2):127–31.
Jahns AC, Lundskog B, Dahlberg I, et al. No link between rosacea and Propionibacterium acnes. APMIS. 2012;120:922–5.
Rihs JD, Brenner DJ, Weaver RE, et al. Roseomonas, a new genus associated with bacteremia and other human infections. J Clin Microbiol. 1993;31(12):3275–83.
Romano-Bertrand S, Bourdier A, Aujoulat F, et al. Skin microbiota is the main reservoir of Roseomonas mucosa, an emerging opportunistic pathogen so far assumed to be environmental. Clin Microbiol Infect. 2016;22(737):e1–7.
Myles IA, Williams KW, Reckhow JD, et al. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016;1(10):1–10.
Myles IA, Earland NJ, Anderson ED, et al. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight. 2018;3(9):1–13.
Tauch A, Fernandez-Natal I, Soriano F. A microbiological and clinical review on Corynebacterium kroppenstedtii. Int J Infect Dis. 2016;48:33–9.
Fujii M, Mizutani Y, Sakuma T, et al. Corynebacterium kroppenstedtii in granulomatous mastitis: analysis of formalin-fixed, paraffin-embedded biopsy specimens by immunostaining using low-specificity bacterial antisera and real-time polymerase chain reaction. Pathol Int. 2018;68(7):409–18.
Johnstone KJ, Robson J, Cherian SG, et al. Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii. Pathology. 2017;49(4):405–12.
Fernandez-Natal I, Rodriguez-Lazaro D, Marrodan-Ciordia T, et al. Characterization and antimicrobial susceptibility of one antibiotic-sensitive and one multidrug-resistant Corynebacterium kroppenstedtii strain isolated from patients with granulomatous mastitis. New Microbes New Infect. 2016;14:93–7.
Johnson MG, Leal S, Plongla R, et al. The brief case: recurrent granulomatous mastitis due to Corynebacterium kroppenstedtii. J Clin Microbiol. 2016;54(8):1938–41.
Riegel P, Leigeois P, Chenard MP, et al. Case report: isolations of Corynebacterium kroppenstedtii from a breast abscess. Int J Med Microbiol. 2004;294(6):413–6.
Poojary I, Kurian A, Jayalekshmi VA, et al. Corynebacterium species causing breast abscesses among patients attending a tertiary care hospital in Chennai, South India. Infect Dis (Lond). 2017;49(7):528–31.
Goh A, Tan AL, Madhukhumar P, Yong WS. Recurrent Corynebacterium kroppenstedtii breast abscess in a young Asian female. Breast J. 2015;21(4):431–2.
Le Fleche-Mateos A, Berthet N, Lomprez F, et al. Case report: recurrent breast abscesses due to Corynebacterium kroppenstedtii, a human pathogen uncommon in Caucasian women. Case Rep Infect Dis. 2012;2012:120968.
Hagemann JB, Essig A, Herrman M, et al. Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii. Int J Med Microbiol. 2015;305:957–9.
Ni Raghallaigh S, Bender K, Lacey N, et al. The fatty acid profile of the skin surface lipid layer in papulopustular rosacea. Br J Dermatol. 2012;166(2):279–87.
Mak TN, Schmid M, Brzuszkiewicz E, et al. Comparative genomics reveals distinct host-interacting traits of three major human-associated Propionibacteria. BMC Genom. 2013;14:640.
Meisel JS, Hannigan GD, Tyldsley AS, SanMiguel AJ, Hodkinson BP, Zheng Q, et al. Skin microbiome surveys are strongly influenced by experimental design. J Investig Dermatol. 2016;146(5):947–56.
Chen CJ, Su LH, Lin TY, Huang YC. Molecular analysis of repeated methicillin-resistant Staphyloccocus aureus infections in children. PLoS One. 2010;5(12):e14431.
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Research reported in this publication was supported by the National Rosacea Society and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under R01AR064297 and AR068280 to Luis A. Garza.
Conflict of interest
Anna L. Chien participated in Galderma’s Rosacea Medical Advisory Board Meeting in 2017. Sewon Kang is an advisory board member of Almirall and has received an honorarium. The participation was not in relation to the current article. Barbara M. Rainer, Katherine G. Thompson, Corina Antonescu, Liliana Florea, Emmanuel F. Mongodin, Jonathan Bui, Helena B. Pasieka, Alexander H. Fischer, and Luis A. Garza have no conflicts of interest that are directly relevant to the content of this article.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Johns Hopkins Institutional Review Board and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Written informed consent was obtained from all participants included in the study.
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Rainer, B.M., Thompson, K.G., Antonescu, C. et al. Characterization and Analysis of the Skin Microbiota in Rosacea: A Case–Control Study. Am J Clin Dermatol 21, 139–147 (2020). https://doi.org/10.1007/s40257-019-00471-5
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DOI: https://doi.org/10.1007/s40257-019-00471-5