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Here, we compared mucosal immune and microbiome responses to experimentally induced mucosal injury between men who have sex with men engaging in receptive anal intercourse (MSM-RAI) and men who do not engage in RAI (controls), all without HIV. Rectal mucosal secretions were collected from adult MSM-RAI (<jats:italic>n<\/jats:italic>\u2009=\u200919) and controls (<jats:italic>n<\/jats:italic>\u2009=\u20096) via anoscopy before and up to eight days after experimentally induced injury. Mucosal healing was evaluated by repeated injury surface area measurements with digital imaging. MSM-RAI demonstrated overall significantly higher concentrations of pro-inflammatory cytokines and a distinct rectal microbiome compared with controls. Wound healing was numerically faster in MSM-RAI but did not meet statistical significance (<jats:italic>p<\/jats:italic>\u2009=\u20090.09). Different cytokine injury response patterns were observed between MSM-RAI and controls; however, IL-6 and IP-10 were important mediators in both groups. Microbial guilds, particularly from the <jats:italic>Lachnospiraceae<\/jats:italic> and <jats:italic>Prevotellaceae<\/jats:italic> families, were associated with rectal mucosal inflammation. This work is the first experimental study of rectal mucosal injury and the immune environment in healthy humans and provides a more nuanced understanding of rectal mucosal inflammation after injury, which can inform our understanding of HIV transmission.<\/jats:p>","DOI":"10.1038\/s41598-024-80074-1","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T18:33:38Z","timestamp":1735583618000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rectal mucosal inflammation, microbiome, and wound healing in men who have sex with men who engage in receptive anal intercourse"],"prefix":"10.1038","volume":"14","author":[{"given":"Vanessa E.","family":"Van Doren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie G.","family":"Ackerley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip M.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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