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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), <jats:italic>in situ<\/jats:italic> hybridization and immunohistochemistry for MCP-1, TNF-\u03b1, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. <jats:italic>In situ<\/jats:italic> hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-\u03b1, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, <jats:italic>Firmicutes<\/jats:italic> was significantly higher in HS than NS. At the genus level, <jats:italic>S. aureus<\/jats:italic> was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Microbiome dysbiosis, dominated by <jats:italic>S. aureus<\/jats:italic>, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1227024","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T19:36:18Z","timestamp":1692819378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiarong","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengding","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiqiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12951","article-title":"Poly(lactide-co-\u03f5-caprolactone) scaffold promotes equivalent tissue integration and supports skin grafts compared to a predicate collagen scaffold","volume":"29","author":"Ruppert","year":"2021","journal-title":"Wound Repair Regen"},{"key":"B2","doi-asserted-by":"publisher","first-page":"110287","DOI":"10.1016\/j.biopha.2020.110287","article-title":"Current potential therapeutic strategies targeting the TGF-\u03b2\/Smad signaling pathway to attenuate keloid and hypertrophic scar formation","volume":"129","author":"Zhang","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B3","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/00006534-200207000-00029","article-title":"Effect of Mederma on hypertrophic scarring in the rabbit ear model","volume":"110","author":"Saulis","year":"2002","journal-title":"Plast Reconstr Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.2002.10606.x","article-title":"Persistent wound infection delays epidermal maturation and increases scarring in thermal burns","volume":"10","author":"Singer","year":"2002","journal-title":"Wound Repair Regen"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/dsu.12474","article-title":"Dynamic hypoxia in scar tissue during human hypertrophic scar progression","volume":"40","author":"Zheng","year":"2014","journal-title":"Dermatol Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12343","article-title":"Severe hypoxia and malnutrition collectively contribute to scar fibroblast inhibition and cell apoptosis","volume":"23","author":"Lynam","year":"2015","journal-title":"Wound Repair Regen"},{"key":"B7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1089\/wound.2016.0709","article-title":"Mechanical forces in cutaneous wound healing: emerging therapies to minimize scar formation","volume":"7","author":"Barnes","year":"2018","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2018.03.004","article-title":"Mechanical forces in skin disorders","volume":"90","author":"Hsu","year":"2018","journal-title":"J Dermatol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.603187","article-title":"The roles of inflammation in keloid and hypertrophic scars","volume":"11","author":"Wang","year":"2020","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181eae781","article-title":"Scarless fetal wound healing: a basic science review","volume":"126","author":"Larson","year":"2010","journal-title":"Plast Reconstr Surg"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803517","article-title":"Soluble TLR2 is present in human amniotic fluid and modulates the intraamniotic inflammatory response to infection","volume":"182","author":"Dulay","year":"2009","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.mehy.2016.09.024","article-title":"Endothelial dysfunction may play a key role in keloid and hypertrophic scar pathogenesis - 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