Alteration in the Skin Microbiome in Cutaneous Graft Versus Host Disease
DOI:
https://doi.org/10.2340/00015555-3613Keywords:
skin microbiome, graft versus host disease, 16S rRNA, Staphylococcus, firmicutesAbstract
Graft versus host disease (GVHD) is a common complication of haematopoietic stem cell transplantation. This study examined the cutaneous microbiome in relation to the pathogenesis of cutaneous GVHD. Bacterial swabs were taken from several sites on 12 patients with cutaneous GVHD. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the MiSeq platform. Microbiome diversity in patients with cutaneous GVHD was reduced compared with healthy controls. GVHD was related to an increased abundance of Firmicutes and a reduction in Actinobacteria, especially in lesions. Non-parametric multivariate analysis of variance revealed that the skin microbial community disorders in patients with GVHD correlated with several clinical features of cutaneous GVHD. This study indicates that changes in the cutaneous microbiota in lesions could play a key role in the pathogenesis of cutaneous GVHD. Further studies are needed to explore the mechanistic relevance of these microbial dynamics, which may provide new clues to therapeutic interventions.
Downloads
References
Abdallah F, Mijouin L, Pichon C. Skin Immune landscape: inside and outside the organism. Mediators Inflamm 2017; 2017: 5095293.
DOI: https://doi.org/10.1155/2017/5095293
Gallo RL, Nakatsuji T. Microbial symbiosis with the innate immune defense system of the skin. J Invest Dermatol 2011; 131: 1974-1980.
DOI: https://doi.org/10.1038/jid.2011.182
Lai Y, Di Nardo A, Nakatsuji T, Leichtle A, Yang Y, Cogen AL, et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat Med 2009; 15: 1377-1382.
DOI: https://doi.org/10.1038/nm.2062
Lai Y, Cogen AL, Radek KA, Park HJ, Macleod DT, Leichtle A, et al. Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections. J Invest Dermatol 2010; 130: 2211-2221.
DOI: https://doi.org/10.1038/jid.2010.123
Clausen ML, Agner T, Lilje B, Edslev SM, Johannesen TB, Andersen PS. Association of disease severity with skin microbiome and filaggrin gene mutations in adult atopic dermatitis. JAMA Dermatol 2018; 154: 293-300.
DOI: https://doi.org/10.1001/jamadermatol.2017.5440
Dagnelie MA, Corvec S, Saint-Jean M, Bourdes V, Nguyen JM, Khammari A, et al. Decrease in diversity of propionibacterium acnes phylotypes in patients with severe acne on the back. Acta Derm Venereol 2018; 98: 262-267.
DOI: https://doi.org/10.2340/00015555-2847
Langan EA, Kunstner A, Miodovnik M, Zillikens D, Thaci D, Baines JF, et al. Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis. Br J Dermatol 2019; 181: 1254-1264.
DOI: https://doi.org/10.1111/bjd.17989
Ganju P, Nagpal S, Mohammed MH, Nishal Kumar P, Pandey R, Natarajan VT, et al. Microbial community profiling shows dysbiosis in the lesional skin of vitiligo subjects. Sci Rep 2016; 6; 18761.
DOI: https://doi.org/10.1038/srep18761
Miodovnik M, Kunstner A, Langan EA, Zillikens D, Glaser R, Sprecher E, et al. A distinct cutaneous microbiota profile in autoimmune bullous disease patients. Exp Dermatol 2017; 26: 1221-1227.
DOI: https://doi.org/10.1111/exd.13357
Huang C, Yi X, Long H, Zhang G, Wu H, Zhao M, et al. Disordered cutaneous microbiota in systemic lupus erythematosus. J Autoimmun 2019; 108: 102391.
DOI: https://doi.org/10.1016/j.jaut.2019.102391
Shlomchik WD. Graft-versus-host disease. Nat Rev Immunol 2007; 7: 340-352.
DOI: https://doi.org/10.1038/nri2000
Goker H, Haznedaroglu IC, Chao NJ. Acute graft-vs-host disease: pathobiology and management. Exp Hematol 2001; 29; 259-277.
DOI: https://doi.org/10.1016/S0301-472X(00)00677-9
Paczesny S, Hanauer D, Sun Y, Reddy P. New perspectives on the biology of acute GVHD. Bone Marrow Transplant 2010; 45: 1-11.
DOI: https://doi.org/10.1038/bmt.2009.328
Noor F, Kaysen A, Wilmes P, Schneider JG. The gut microbiota and hematopoietic stem cell transplantation: challenges and potentials. J Innate Immun 2019; 11: 405-415.
DOI: https://doi.org/10.1159/000492943
Shono Y, Docampo MD, Peled JU, Perobelli SM, Jenq RR. Intestinal microbiota-related effects on graft-versus-host disease. Int J Hematol 2015; 101: 428-437.
DOI: https://doi.org/10.1007/s12185-015-1781-5
Murphy S, Nguyen VH. Role of gut microbiota in graft-versus-host disease. Leuk Lymphoma 2011; 52: 1844-1856.
DOI: https://doi.org/10.3109/10428194.2011.580476
Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014; 20: 640-645.
DOI: https://doi.org/10.1016/j.bbmt.2014.01.030
Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 2012; 209: 903-911.
DOI: https://doi.org/10.1084/jem.20112408
Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500: 232-236.
DOI: https://doi.org/10.1038/nature12331
Lei YM, Sepulveda M, Chen L, Wang Y, Pirozzolo I, Theriault B, et al. Skin-restricted commensal colonization accelerates skin graft rejection. JCI Insight 2019; 5: e127569.
DOI: https://doi.org/10.1172/jci.insight.127569
Robinson CJ, Bohannan BJ, Young VB. From structure to function: the ecology of host-associated microbial communities. Microbiol Mol Biol Rev 2010; 74: 453-476.
DOI: https://doi.org/10.1128/MMBR.00014-10
Kong HH. Skin microbiome: genomics-based insights into the diversity and role of skin microbes. Trends Mol Med 2011; 17: 320-328.
DOI: https://doi.org/10.1016/j.molmed.2011.01.013
Fadrosh DW, Ma B, Gajer P, Sengamalay N, Ott S, Brotman RM, et al. An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform. Microbiome 2014; 2: 6.
DOI: https://doi.org/10.1186/2049-2618-2-6
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30: 2114-2120.
DOI: https://doi.org/10.1093/bioinformatics/btu170
Magoc T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 2011; 27: 2957-2963.
DOI: https://doi.org/10.1093/bioinformatics/btr507
Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010; 26: 2460-2461.
DOI: https://doi.org/10.1093/bioinformatics/btq461
MetaStats 2.0 package": White JR, Nagarajan N, Pop M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol 2009; 5: e1000352.
DOI: https://doi.org/10.1371/journal.pcbi.1000352
Chang HW, Yan D, Singh R, Liu J, Lu X, Ucmak D, et al. Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. Microbiome 2018; 6: 154.
DOI: https://doi.org/10.1186/s40168-018-0533-1
The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2013; 486: 207-214.
DOI: https://doi.org/10.1038/nature11234
Hamady 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: 17-27.
DOI: https://doi.org/10.1038/ismej.2009.97
Brestoff JR, Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol 2013; 14: 676-684.
DOI: https://doi.org/10.1038/ni.2640
Kosiewicz MM, Zirnheld AL, Alard P. Tuning of skin immunity by skin commensal bacteria. Immunotherapy 2013; 5: 23-25.
DOI: https://doi.org/10.2217/imt.12.140
Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 2014; 124: 1174-1182.
DOI: https://doi.org/10.1182/blood-2014-02-554725
Rosenbaum JT, Silverman GJ. The microbiome and systemic lupus erythematosus. N Engl J Med 2018; 378: 2236-2237.
DOI: https://doi.org/10.1056/NEJMcibr1804368
Charlson ES, Diamond JM, Bittinger K, Fitzgerald AS, Yadav A, Haas AR, et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am J Respir Crit Care Med 2012; 186: 536-545.
DOI: https://doi.org/10.1164/rccm.201204-0693OC
Oh PL, Martinez I, Sun Y, Walter J, Peterson DA, Mercer DF. Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am J Transplant 2012; 12: 753-762.
DOI: https://doi.org/10.1111/j.1600-6143.2011.03860.x
Han L, Jin H, Zhou L, Zhang X, Fan Z, Dai M, et al. Intestinal microbiota at engraftment influence acute graft-versus-host disease via the Treg/Th17 balance in allo-HSCT recipients. Front Immunol 2018; 9: 669.
DOI: https://doi.org/10.3389/fimmu.2018.00669
Li K, Mu Z, Wen G, Zhao Y, Cong X, Zhang J. Increased Treg cells and eosinophils characterize atopic dermatitis-like graft-versus-host disease compared to lichen planus-like graft-versus host disease. J Am Acad Dermatol 2020; 83: 824-831.
DOI: https://doi.org/10.1016/j.jaad.2019.08.005
Reinhardt K, Foell D, Vogl T, Mezger M, Wittkowski H, Fend F, et al. Monocyte-induced development of Th17 cells and the release of S100 proteins are involved in the pathogenesis of graft-versus-host disease. J Immunol 2014; 193: 3355-3365.
DOI: https://doi.org/10.4049/jimmunol.1400983
Varelias A, Ormerod KL, Bunting MD, Koyama M, Gartlan KH, Kuns RD, et al. Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood 2017; 129: 2172-2185.
DOI: https://doi.org/10.1182/blood-2016-08-732628
Quan C, Chen XY, Li X, Xue F, Chen LH, Liu N, et al. Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium. J Am Acad Dermatol 2020; 82: 955-961.
DOI: https://doi.org/10.1016/j.jaad.2019.06.024
Ahmed EB, Wang T, Daniels M, Alegre ML, Chong AS. IL-6 induced by Staphylococcus aureus infection prevents the induction of skin allograft acceptance in mice. Am J Transplant 2011; 11: 936-946.
DOI: https://doi.org/10.1111/j.1600-6143.2011.03476.x
Wang T, Ahmed EB, Chen L, Xu J, Tao J, Wang CR, et al. Infection with the intracellular bacterium, Listeria monocytogenes, overrides established tolerance in a mouse cardiac allograft model. Am J Transplant 2010; 10: 1524-1533.
DOI: https://doi.org/10.1111/j.1600-6143.2010.03066.x
Fyhrquist N, Ruokolainen L, Suomalainen A, Lehtimaki S, Veckman V, Vendelin J, et al. Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation. J Allergy Clin Immunol 2014; 134: 1301-1309 e1311.
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 Ying Gu, Jing Sun, Kun Li, Xia Wu, Jianzhong Zhang
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.