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Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage \u03c6PaP11-13 attenuating\n            <jats:italic>C. acnes<\/jats:italic>\n            -induced inflammation in rat models. We found that rats infected with\n            <jats:italic>C. acnes<\/jats:italic>\n            had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin\u2013eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with\n            <jats:italic>C. acnes<\/jats:italic>\n            , which was decreased after the application of phage \u03c6PaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of\n            <jats:italic>C. acnes<\/jats:italic>\n            -induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K\/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after\n            <jats:italic>C. acnes<\/jats:italic>\n            infection. Subsequently, it was shown that the activation of the PI3K\/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage \u03c6PaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by\n            <jats:italic>C. acnes<\/jats:italic>\n            and phage \u03c6PaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage \u03c6PaP11-13 is lysing\n            <jats:italic>C. acnes<\/jats:italic>\n            and regulating keratinocyte apoptosis via the PI3K\/Akt signaling pathway.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Cutibacterium acnes<\/jats:italic>\n              infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating\n              <jats:italic>Cutibacterium acnes<\/jats:italic>\n              . Bacteriophages are currently proven effective in MDR (multiple drug-resistant)\n              <jats:italic>Cutibacterium acnes<\/jats:italic>\n              , but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing\n              <jats:italic>Cutibacterium acnes<\/jats:italic>\n              . However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among \"phage\u2013bacteria\u2013host\" inspires huge interest in future phage therapy studies.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02838-23","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T14:01:06Z","timestamp":1704895266000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Application of bacteriophage \u03c6PaP11-13 attenuates rat\n            <i>Cutibacterium acnes<\/i>\n            infection lesions by promoting keratinocytes apoptosis via inhibiting PI3K\/Akt pathway"],"prefix":"10.1128","volume":"12","author":[{"given":"Yuanyuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Army Medical University (the Third Military Medical University), Chongqing, China"},{"name":"Cadet Brigade 4, College of Basic Medicine, Army Medical 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