Abstract
Melanoma is the least common form of skin tumor, but it is potentially the most dangerous and responsible for the majority of skin cancer deaths. We suggest that the skin microbiome might be changed during the progression of melanoma. The aim of this study is to compare the composition of the skin microbiota between different locations (skin and melanoma) of a MeLiM (Melanoma-bearing Libechov Minipig) pig model (exophytic melanoma). Ninety samples were used for PCR-DGGE analysis with primers specifically targeting the V3 region of the 16S rRNA gene. The profiles were used for cluster analysis by UPGMA and principal coordinate analysis PCoA and also to calculate the diversity index (Simpson index of diversity). By comparing the obtained results, we found that both bacterial composition and diversity were significantly different between the skin and melanoma microbiomes. The abundances of Fusobacterium and Trueperella genera were significantly increased in melanoma samples, suggesting a strong relationship between melanoma development and skin microbiome changes.
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Asoudeh-Fard A, Barzegari A, Dehnad A, Bastani S, Golchin A, Omidi Y (2017) Lactobacillus plantarum induces apoptosis in oral cancer KB cells through up regulation of PTEN and downregulation of MAPK signalling pathways. Bioimpacts 7:193–198. https://doi.org/10.15171/bi.2017.22
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206. https://doi.org/10.1200/JCO.2009.23.4799
Byrd AL, Belkaid Y, Segre JS (2018) The human skin microbiome. Nat Rev Microbiol 16:143–155. https://doi.org/10.1038/nrmicro.2017.157
Casanova C, Iselin L, von Steiger N, Droz S, Sendi P (2011) Staphylococcus hyicus bacteremia in a farmer. J Clin Microbiol 49:4377–4378. https://doi.org/10.1128/JCM.05645-11
Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, Holt RA (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:299–306. https://doi.org/10.1101/gr.126516.111
Cheng Z, Xu H, Wang X, Liu Z (2017) Lactobacillus raises in vitro anticancer effect of geniposide in HSC-3 human oral squamous cell carcinoma cells. Exp Ther Med 5:4586–4594. https://doi.org/10.15171/bi.2017.22
Cutler K, Chu P, Levin M, Wallack M, Don PC, Weinberg JM (2000) Pedunculated malignant melanoma. Dermatol Surg 26:127–129. https://doi.org/10.1046/j.1524-4725.2000.99092.x
Dethlefsen L, McFall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature 449:811–818. https://doi.org/10.1038/nature06245
Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, Bruha J, Neary P, Dezeeuw N, Tommasino M, Jenab M, Prehn JHM, Hughes DJ (2014) Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 33:1381–1390. https://doi.org/10.1007/s10096-014-2081-3
Gallimidi AB, Fischman S, Revach B, Bulvik R, Maliutina A, Rubinstein AM, Nussbaum G, Elkin M (2015) Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 6:22613–22623. https://doi.org/10.18632/oncotarget.4209
Grice EA, Kong H, Conlan S, Deming CB, Davis J, Young AC, NISC Comparative Sequencing Program, Bouffard G, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA (2009) Topographical and temporal diversity of the human skin microbiome. Science 324:1190–1192. https://doi.org/10.1126/science.1171700
Grice EA, Snitkin ES, Yockey LJ, Bermudez DM, Liechty KW, Segre JA (2010) Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proc Natl Acad Sci U S A 107:14799–14804. https://doi.org/10.1073/pnas.1004204107
Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, Gamliel M, Enk J, Bar-On Y, Stanietsky-Kaynan N, Coppenhagen-Glazer S, Shussman N, Almogy G, Cuapio A, Hofer E, Mevorach D, Tabib A, Ortenberg R, Markel G, Miklić K, Jonjic S, Brennan CA, Garrett WS, Bachrach G, Mandelboim O (2015) Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344–355. https://doi.org/10.1016/j.immuni.2015.01.010
Hikawa RS, Kanehisa ES, Enokihara MMSS, Enokihara MY, Hirata SH (2014) Polypoid melanoma and superficial spreading melanoma—different subtypes in the same lesion. An Bras Dermatol 89:666–668. https://doi.org/10.1590/abd1806-4841.20142802
Holt RA, Cochrane K (2017) Tumor potentiating mechanisms of Fusobacterium nucleatum, a multifaceted microbe. Gastroenterology 152:694–696. https://doi.org/10.1053/j.gastro.2017.01.024
Hughes JM, Wilson ME, Brandt CM, Spellerberg B (2009) Human infections due to Streptococcus dysgalactiae subspecies equisimilis. Clin Infect Dis 49:766–772. https://doi.org/10.1086/605085
Jacouton E, Chain F, Sokol H, Langella P, Bermúdez-Humarán LG (2017) Probiotic strain Lactobacillus casei BL23 prevents colitis-associated colorectal cancer. Front Immunol 8:1553. https://doi.org/10.3389/fimmu.2017.01553
Jarosz ŁS, Grądzki Z, Kalinowski M (2014) Trueperella pyogenes infections in swine: clinical course and pathology. Pol J Vet Sci 17:395–404. https://doi.org/10.2478/pjvs-2014-0055
Kaczor T, Fabno ND (2017) The human microbiome in cancer: a mini-review of microbiome optimization in oncology. Natural Medicine Journal 9:20–27
Kasuya K, Yoshida E, Harada R, Hasegawa M, Osaka H, Kato M, Shibahara T (2014) Systemic Streptococcus dysgalactiae subspecies equisimilis infection in a Yorkshire pig with severe disseminated suppurative Meningo-encephalomyelitis. J Vet Med Sci 76:715–718. https://doi.org/10.1292/jvms.13-0526
Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Birren BW, Huttenhower C, Garrett WS, Meyerson M (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298. https://doi.org/10.1101/gr.126573.111
Larsen AM, Bullard SA, Womble M, Arias CR (2015) Community structure of skin microbiome of gulf killifish, Fundulus grandis, is driven by seasonality and not exposure to oiled sediments in a Louisiana salt marsh. Microb Ecol 70:534–544. https://doi.org/10.1007/s00248-015-0578-7
Li W, Han L, Yu P, Ma C, Wu X, Moore JE, Xu J (2014) Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers. Microb Ecol 67:735–986. https://doi.org/10.1007/s00248-013-0345-6
Madden TL, Tatusov RL, Zhang J (1996) Applications of network BLAST server. Methods Enzymol 266:131–141. https://doi.org/10.1016/S0076-6879(96)66011-X
Marschalek J, Farr A, Marschalek ML, Domig KJ, Kneifel W, Singer CF, Kiss H, Petricevic L (2017) Influence of orally administered probiotic Lactobacillus strains on vaginal microbiota in women with breast cancer during chemotherapy: a randomized placebo-controlled double-blinded pilot study. Breast Care (Basel) 5:335–339. https://doi.org/10.1159/000478994
McGovern VJ, Mihm MC Jr, Bailly C, Booth JC, Clark WH Jr, Cochran AJ, Hardy EG, Hicks JD, Levene A, Lewis MG, Little JH, Milton GW (1973) The classification of malignant melanoma and its histologic reporting. Cancer 32:1446–1457. https://doi.org/10.1002/1097-0142(197312)32:6<1446::AID-CNCR2820320623>3.0.CO;2-8
McIntyre MK, Peacock TJ, Akers KS, Burmeister DM (2016) Initial characterization of the pig skin bacteriome and its effect on In Vitro models of wound healing. PLoS One 11:e0166176. https://doi.org/10.1371/journal.pone.0166176
Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, Tachibana M, Tanuma T, Maguchi H, Shinohara T, Hasegawa T, Imamura M, Kimura Y, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y (2015) Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 6:7209–7220. https://doi.org/10.18632/oncotarget.3109
Motevaseli E, Azam R, Akrami SM, Mazlomy M, Saffari M, Modarressi MH, Daneshvar M, Ghafouri-Fard S (2016) The effect of lactobacillus crispatus and lactobacillus rhamnosus culture supernatants on expression of autophagy genes and HPV E6 and E7 oncogenes in the HeLa cell line. Cell J (Yakhteh) 17:601–607. https://doi.org/10.22074/cellj.2016.3833
Motevaseli E, Dianatpour A, Ghafouri-Fard S (2017) The role of probiotics in cancer treatment: emphasis on their in vivo and in vitro anti-metastatic effects. Int J Mol Cell Med 6:66–76. https://doi.org/10.22088/acadpub.BUMS.6.2.1
Motevaseli E, Khorramizadeh MR, Hadjati J, Bonab SF, Eslami S, Ghafouri-Fard S (2018) Investigation of antitumor effects of Lactobacillus crispatus in experimental model of breast cancer in BALB/c mice. Immunotherapy 10:119–129. https://doi.org/10.2217/imt-2017-0088
Muyzer G, Dewaal EC, Uitterlinden AG (1993) Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol 59:695–700
Nagano Y, Watabe M, Porter KG, Coulter WA, Millar BC, Elborn JS, Goldsmith CE, Rooney PJ, Loughrey A, Moore JE (2016) Development of a genus-specific PCR assay for the molecular detection, confirmation and identification of Fusobacterium spp. Br J Biomed Sci 64:74–77. https://doi.org/10.1080/09674845.2007.11732760
Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y (2012) Compartmentalized control of skin immunity by resident commensals. Science 337:1115–1119. https://doi.org/10.1126/science.1225152
Nakatsuji T, Chiang HI, Jiang SB, Nagarajan H, Zengler K, Gallo RL (2013) The microbiome extends to subepidermal compartments of normal skin. Nat Commun 4:1431–1431. https://doi.org/10.1038/ncomms2441
Nakatsuji T, Chen TH, Butcher AM, Trzoss LL, Nam S-J, Shirakawa KT, Zhou W, Oh J, Otto M, Fenical W, Gallo RL (2018) A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci Adv 4:eaao4502, 1–9. https://doi.org/10.1126/sciadv.aao4502
Park J, Friendship RM, Poljak Z, Weese JS, Dewey CE (2013) An investigation of exudative epidermitis (greasy pig disease) and antimicrobial resistance patterns of Staphylococcus hyicus and Staphylococcus aureus isolated from clinical cases. Can Vet J 54:139–144
Rasouli BS, Ghadimi-Darsajini A, Nekouian R, Iragian GR (2017) In vitro activity of probiotic Lactobacillus reuteri against gastric cancer progression by downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor gene expression. J Cancer Res Ther 13:246–251. https://doi.org/10.4103/0973-1482.204897
Rodrigues Hoffmann A, Patterson AP, Diesel A, Lawhon SD, Ly HJ, Stephenson CE, Mansell J, Steiner JM, Dowd SE, Olivry T, Suchodolski JS (2014) The skin microbiome in healthy and allergic dogs. PLoS One 9:e83197. https://doi.org/10.1371/journal.pone.0083197
Roy S, Trinchieri G (2017) Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer 17:271–285. https://doi.org/10.1038/nrc.2017.13
Salava A, Aho V, Pereira P, Koskinen K, Paulin L, Auvinen P, Lauerma A (2016) Skin microbiome in melanomas and melanocytic nevi. Eur J Dermatol 26:49–55. https://doi.org/10.1684/ejd.2015.2696
Sanford JA, Gallo RL (2013) Functions of the skin microbiota in health and disease. Semin Immunol 25:370–377. https://doi.org/10.1016/j.smim.2013.09.005
Smeekens SP, Huttenhower C, Riza A, Van De Veerdonk F, Zeeuwen PL, Schalkwijk J, Van Der Meer JW, Xavier RJ, Netea MG, Gevers D (2014) Skin microbiome imbalance in patients with STAT1/STAT3 defects impairs innate host defense responses. J. Innate Immun 6:253–262. https://doi.org/10.1159/000351912
Walke JB, Becker MH, Loftus SC, House LL, Cormier G, Jensen RV, Belden LK (2014) Amphibian skin may select for rare environmental microbes. ISME J 8:2207–2217. https://doi.org/10.1038/ismej.2014.77
Yang X, Da M, Zhang W, Qi Q, Zhang C, Han S (2018) Role of Lactobacillus in cervical cancer. Cancer Manag Res 10:1219–1229. https://doi.org/10.2147/CMAR.S165228
Zeng B, Zhao J, Guo W, Zhang S, Hua Y, Tang J, Kong F, Yang X, Fu L, Liao K, Yu X, Chen G, Jin L, Shuai S, Yang J, Si X, Ning R, Mishra S, Li Y (2017) High-altitude living shapes the skin microbiome in humans and pigs. Front Microbiol 8:1929. https://doi.org/10.3389/fmicb.2017.01929
Zhao K, Liu M, Zhang X, Wang H, Yue B (2013) In vitro and in vivo expression of virulence genes in Trueperella pyogenes based on a mouse model. Vet Microbiol 163:344–350. https://doi.org/10.1016/j.vetmic.2013.01.019
Acknowledgements
This work was supported by grants CIGA 20162019 and 20162001 of the Grant Agency of Czech University of Life Sciences Prague, Project Excellence CZ.02.1.01/0.0/0.0/15_003/0000460 and also by the Ministry of Education, Youth and Sports of the Czech Republic (project number LO1609) under the NPU I program.
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Mrázek, J., Mekadim, C., Kučerová, P. et al. Melanoma-related changes in skin microbiome. Folia Microbiol 64, 435–442 (2019). https://doi.org/10.1007/s12223-018-00670-3
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DOI: https://doi.org/10.1007/s12223-018-00670-3