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Their pathophysiology remains poorly defined, but as with other chronic wounds, it is hypothesised that the microbial milieu, or microbiome, contributes to their healing and clinical outcomes. This study utilises 16S ribosomal RNA (rRNA) gene sequencing to describe, for the first time, the microbiome of the SCD leg ulcer and its association with clinical factors. In a cross\u2010sectional analysis of 42 ulcers, we recovered microbial profiles similar to other chronic wounds in the predominance of anaerobic bacteria and opportunistic pathogens including <jats:italic>Staphylococcus<\/jats:italic>, <jats:italic>Corynebacterium<\/jats:italic>, and <jats:italic>Finegoldia<\/jats:italic>. Ulcers separated into two clusters: one defined by predominance of <jats:italic>Staphylococcus<\/jats:italic> and smaller surface area, and the other displaying a greater diversity of taxa and larger surface area. We also find that the relative abundance of <jats:italic>Porphyromonas<\/jats:italic> is negatively associated with haemoglobin levels, a key clinical severity indicator for SCD, and that <jats:italic>Finegoldia<\/jats:italic> relative abundance is negatively associated with CD19+ B cell count. Finally, ratios of <jats:italic>Corynebacterium<\/jats:italic>:<jats:italic>Lactobacillus<\/jats:italic> and <jats:italic>Staphylococcus<\/jats:italic>:<jats:italic>Lactobacillus<\/jats:italic> are elevated in the intact skin of individuals with a history of SCD leg ulcers, while the ratio of <jats:italic>Lactobacillus<\/jats:italic>:<jats:italic>Bacillus<\/jats:italic> is elevated in that of individuals without a history of ulcers. Investigations of the skin microbiome in relation to SCD ulcer pathophysiology can inform clinical guidelines for this poorly understood chronic wound, as well as enhance broader understanding about the role of the skin microbiome in delayed wound healing.<\/jats:p>","DOI":"10.1111\/wrr.12924","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T07:43:09Z","timestamp":1620546189000},"page":"801-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Insights into the skin microbiome of sickle cell disease leg ulcers"],"prefix":"10.1111","volume":"29","author":[{"given":"Julia","family":"Byeon","sequence":"first","affiliation":[{"name":"Social and Behavioral Research Branch National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine 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