{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:53:55Z","timestamp":1787169235511,"version":"build-2736575974"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 HL111130"],"award-info":[{"award-number":["R01 HL111130"]}]},{"name":"National Institute of Health","award":["T32CA009501"],"award-info":[{"award-number":["T32CA009501"]}]},{"name":"Cancer Center Support Grant","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Lymphedema is a chronic condition that commonly occur from lymphatic injury following surgical resection of solid malignancies. While many studies have centered on the molecular and immune pathways that perpetuate lymphatic dysfunction, the role of the skin microbiome in lymphedema development remains unclear. In this study, skin swabs collected from normal and lymphedema forearms of 30 patients with unilateral upper extremity lymphedema were analyzed by 16S ribosomal RNA sequencing. Statistical models for microbiome data were utilized to correlate clinical variables with microbial profiles. Overall, 872 bacterial taxa were identified. There were no significant differences in microbial alpha diversity of the colonizing bacteria between normal and lymphedema skin samples (p = 0.25). Notably, for patients without a history of infection, a one-fold change in relative limb volume was significantly associated with a 0.58-unit increase in Bray-Curtis microbial distance between paired limbs (95%CI = 0.11,1.05, p = 0.02). Additionally, several genera, including\n                    <jats:italic>Propionibacterium<\/jats:italic>\n                    and\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    , demonstrated high variability between paired samples. In summary, we demonstrate high compositional heterogeneity in the skin microbiome in upper extremity secondary lymphedema, supporting future studies into the role of host-microbe interactions on lymphedema pathophysiology.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0283609","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T13:36:27Z","timestamp":1684330587000},"page":"e0283609","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Skin microbiome alterations in upper extremity secondary lymphedema"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-9859","authenticated-orcid":true,"given":"Adana-Christine","family":"Campbell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Eun","family":"Baik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeung Ju","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyeon","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Kuonqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stav","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananta","family":"Sarker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu P.","family":"Kataru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5717-697X","authenticated-orcid":true,"given":"Babak J.","family":"Mehrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"issue":"7","key":"pone.0283609.ref001","article-title":"Histopathologic Features of Lymphedema: A Molecular Review.","volume":"21","author":"CY Li","year":"2020","journal-title":"Int J Mol Sci."},{"key":"pone.0283609.ref002","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fimmu.2019.00076","article-title":"Modulation of Immunity by Lymphatic Dysfunction in Lymphedema.","volume":"10","author":"Y Yuan","year":"2019","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0283609.ref003","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jvsv.2021.04.009","article-title":"Cellulitis risk factors for patients with primary or secondary lymphedema","volume":"10","author":"S Vignes","year":"2022","journal-title":"J Vasc Surg Venous Lymphat Disord"},{"issue":"1","key":"pone.0283609.ref004","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12010135","article-title":"Preoperative Assessment of Upper Extremity Secondary Lymphedema.","volume":"12","author":"I Wiser","year":"2020","journal-title":"Cancers (Basel)."},{"key":"pone.0283609.ref005","doi-asserted-by":"crossref","first-page":"9377","DOI":"10.1186\/1757-1626-2-9377","article-title":"Challenges of cellulitis in a lymphedematous extremity: a case report.","volume":"2","author":"MP Connor","year":"2009","journal-title":"Cases J."},{"key":"pone.0283609.ref006","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.suronc.2020.09.005","article-title":"Epidemiology of Lymphedema-related admissions in the United States: 2012\u20132017.","volume":"35","author":"M Lopez","year":"2020","journal-title":"Surg Oncol."},{"issue":"2","key":"pone.0283609.ref007","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jid.2017.09.011","article-title":"Regulatory T Cells Mediate Local Immunosuppression in Lymphedema","volume":"138","author":"GD Garc\u00eda Nores","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"12","key":"pone.0283609.ref008","doi-asserted-by":"crossref","first-page":"e0168259","DOI":"10.1371\/journal.pone.0168259","article-title":"Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema.","volume":"11","author":"JJ Huang","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"pone.0283609.ref009","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00424-016-1903-9","article-title":"Tight junctions in skin inflammation","volume":"469","author":"K B\u00e4sler","year":"2017","journal-title":"Pflugers Arch"},{"key":"pone.0283609.ref010","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fimmu.2015.00353","article-title":"Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang of Cutaneous Inflammation.","volume":"6","author":"T Biedermann","year":"2015","journal-title":"Front Immunol"},{"issue":"6","key":"pone.0283609.ref011","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.jid.2016.11.045","article-title":"Human Skin Is the Largest Epithelial Surface for Interaction with Microbes","volume":"137","author":"RL Gallo","year":"2017","journal-title":"J Invest Dermatol"},{"issue":"7","key":"pone.0283609.ref012","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/01.ASW.0000520501.23702.82","article-title":"Skin and Wound Care in Lymphedema Patients: A Taxonomy, Primer, and Literature Review.","volume":"30","author":"CE Fife","year":"2017","journal-title":"Adv Skin Wound Care."},{"issue":"3","key":"pone.0283609.ref013","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.anai.2018.12.003","article-title":"The role of the skin microbiome in atopic dermatitis","volume":"122","author":"T Nakatsuji","year":"2019","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"7","key":"pone.0283609.ref014","doi-asserted-by":"crossref","first-page":"e2719","DOI":"10.1371\/journal.pone.0002719","article-title":"Substantial alterations of the cutaneous bacterial biota in psoriatic lesions.","volume":"3","author":"Z Gao","year":"2008","journal-title":"PLoS One"},{"issue":"4","key":"pone.0283609.ref015","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/jocd.14273","article-title":"Psoriasis: Embarking a dynamic shift in the skin microbiota.","volume":"21","author":"M Gupta","year":"2022","journal-title":"J Cosmet Dermatol"},{"issue":"5","key":"pone.0283609.ref016","doi-asserted-by":"crossref","first-page":"e01315","DOI":"10.1128\/mBio.01315-15","article-title":"The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection.","volume":"6","author":"JJ van Rensburg","year":"2015","journal-title":"mBio"},{"issue":"12","key":"pone.0283609.ref017","doi-asserted-by":"crossref","first-page":"adv00164","DOI":"10.2340\/00015555-3514","article-title":"Skin Microbiome in Atopic Dermatitis.","volume":"100","author":"SM Edslev","year":"2020","journal-title":"Acta Derm Venereol."},{"issue":"11","key":"pone.0283609.ref018","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11882-015-0567-4","article-title":"The role of the skin microbiome in atopic dermatitis","volume":"15","author":"MR Williams","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"issue":"8","key":"pone.0283609.ref019","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00018-014-1812-z","article-title":"Interactions between host factors and the skin microbiome","volume":"72","author":"A SanMiguel","year":"2015","journal-title":"Cell Mol Life Sci"},{"issue":"7","key":"pone.0283609.ref020","doi-asserted-by":"crossref","DOI":"10.1172\/JCI154944","article-title":"Next-generation sequencing: insights to advance clinical investigations of the microbiome","volume":"132","author":"CR Wensel","year":"2022","journal-title":"J Clin Invest"},{"key":"pone.0283609.ref021","doi-asserted-by":"crossref","first-page":"e01237","DOI":"10.1016\/j.sciaf.2022.e01237","article-title":"Shift in the skin microbiome among individuals presenting with filarial lymphedema compared to non-filarial healthy individuals in Ghana.","volume":"16","author":"A Kwarteng","year":"2022","journal-title":"Scientific African."},{"issue":"8","key":"pone.0283609.ref022","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"E Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"issue":"7","key":"pone.0283609.ref023","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data.","volume":"13","author":"BJ Callahan","year":"2016","journal-title":"Nat Methods"},{"issue":"3","key":"pone.0283609.ref024","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/ismej.2011.139","article-title":"An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.","volume":"6","author":"D McDonald","year":"2012","journal-title":"Isme j"},{"issue":"1","key":"pone.0283609.ref025","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s40168-021-01034-9","article-title":"Constraining PERMANOVA and LDM to within-set comparisons by projection improves the efficiency of analyses of matched sets of microbiome data.","volume":"9","author":"Z Zhu","year":"2021","journal-title":"Microbiome."},{"issue":"23","key":"pone.0283609.ref026","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1093\/bioinformatics\/btr568","article-title":"Sequential Monte Carlo multiple testing","volume":"27","author":"GK Sandve","year":"2011","journal-title":"Bioinformatics"},{"key":"pone.0283609.ref027","volume-title":"Lymphedema. StatPearls","author":"BC Sleigh","year":"2022"},{"issue":"5","key":"pone.0283609.ref028","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/MIB.0000000000000750","article-title":"Current Understanding of Dysbiosis in Disease in Human and Animal Models.","volume":"22","author":"AK DeGruttola","year":"2016","journal-title":"Inflamm Bowel Dis."},{"issue":"2","key":"pone.0283609.ref029","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/ilar\/ilv017","article-title":"Analyses of Intestinal Microbiota: Culture versus Sequencing.","volume":"56","author":"A Hiergeist","year":"2015","journal-title":"Ilar j."},{"key":"pone.0283609.ref030","doi-asserted-by":"crossref","first-page":"105047","DOI":"10.1016\/j.psyneuen.2020.105047","article-title":"Volatility as a Concept to Understand the Impact of Stress on the Microbiome.","volume":"124","author":"TFS Bastiaanssen","year":"2021","journal-title":"Psychoneuroendocrinology."},{"issue":"5","key":"pone.0283609.ref031","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/gb-2011-12-5-114","article-title":"The volatile microbiome","volume":"12","author":"GM Weinstock","year":"2011","journal-title":"Genome Biol"},{"key":"pone.0283609.ref032","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1038\/nmicrobiol.2017.4","article-title":"Dynamics of the human gut microbiome in inflammatory bowel disease","volume":"2","author":"J Halfvarson","year":"2017","journal-title":"Nat Microbiol"},{"issue":"5","key":"pone.0283609.ref033","article-title":"Gut-Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis.","volume":"10","author":"AY Thye","year":"2022","journal-title":"Biomedicines"},{"issue":"2","key":"pone.0283609.ref034","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/lrb.2009.0004","article-title":"The psycho-social impact of lymphedema.","volume":"7","author":"SH Ridner","year":"2009","journal-title":"Lymphat Res Biol"},{"issue":"1","key":"pone.0283609.ref035","doi-asserted-by":"crossref","first-page":"e0190231","DOI":"10.1371\/journal.pone.0190231","article-title":"The effect of relaxation techniques on edema, anxiety and depression in post-mastectomy lymphedema patients undergoing comprehensive decongestive therapy: A clinical trial.","volume":"13","author":"B Abbasi","year":"2018","journal-title":"PLoS One"},{"issue":"424","key":"pone.0283609.ref036","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam7964","article-title":"Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic vessel dysfunction.","volume":"10","author":"D Jones","year":"2018","journal-title":"Sci Transl Med."},{"issue":"12","key":"pone.0283609.ref037","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.tim.2013.10.001","article-title":"Structure and function of the human skin microbiome","volume":"21","author":"NN Schommer","year":"2013","journal-title":"Trends Microbiol"},{"issue":"8","key":"pone.0283609.ref038","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1073\/pnas.0607077104","article-title":"Molecular analysis of human forearm superficial skin bacterial biota","volume":"104","author":"Z Gao","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0283609.ref039","doi-asserted-by":"crossref","first-page":"R101","DOI":"10.1186\/gb-2012-13-11-r101","article-title":"Microbiome dynamics of human epidermis following skin barrier disruption","volume":"13","author":"PL Zeeuwen","year":"2012","journal-title":"Genome Biol"},{"issue":"5960","key":"pone.0283609.ref040","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1126\/science.1177486","article-title":"Bacterial community variation in human body habitats across space and time","volume":"326","author":"EK Costello","year":"2009","journal-title":"Science"},{"issue":"5","key":"pone.0283609.ref041","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.clindermatol.2011.03.003","article-title":"Opportunistic localization of skin lesions on vulnerable areas.","volume":"29","author":"V Ruocco","year":"2011","journal-title":"Clin Dermatol"},{"issue":"4","key":"pone.0283609.ref042","first-page":"177","article-title":"Lymphoscintigraphic evaluation in patients after erysipelas.","volume":"33","author":"JM de Godoy","year":"2000","journal-title":"Lymphology."},{"issue":"6","key":"pone.0283609.ref043","doi-asserted-by":"crossref","first-page":"e38182","DOI":"10.1371\/journal.pone.0038182","article-title":"Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs.","volume":"7","author":"M Mihara","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"pone.0283609.ref044","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbz155","article-title":"Current challenges and best-practice protocols for microbiome analysis","volume":"22","author":"R Bharti","year":"2021","journal-title":"Brief Bioinform"},{"key":"pone.0283609.ref045","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3389\/fmicb.2019.00438","article-title":"Dysbiosis of Skin Microbiota in Psoriatic Patients: Co-occurrence of Fungal and Bacterial Communities.","volume":"10","author":"Z Stehlikova","year":"2019","journal-title":"Front Microbiol."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283609","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T13:37:17Z","timestamp":1684330637000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283609"}},"subtitle":[],"editor":[{"given":"Jos\u00e9 Ant\u00f3nio Baptista","family":"Machado Soares","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0283609","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}