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In this pilot study, we used a multiomics approach to explore the host\u2013microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however <jats:italic>Staphylococcus aureus<\/jats:italic> and <jats:italic>Streptococcus<\/jats:italic> genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both <jats:italic>Staphylococcus aureus<\/jats:italic> and <jats:italic>Streptococcus<\/jats:italic>. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.<\/jats:p>","DOI":"10.1038\/s41522-021-00202-x","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:03:43Z","timestamp":1616411023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study"],"prefix":"10.1038","volume":"7","author":[{"given":"Michael","family":"Radzieta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemah","family":"Sadeghpour-Heravi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-4089","authenticated-orcid":false,"given":"Honghua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vickery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jeffries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh G.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-8031","authenticated-orcid":false,"given":"Saskia","family":"Schwarzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slade O.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Malone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"202_CR1","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","volume":"15","author":"DG Armstrong","year":"2017","unstructured":"Armstrong, D. 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