{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:28:59Z","timestamp":1790040539572,"version":"4.0.1"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Trade, Industry & Energy (MOTIE, Republic of Korea).","award":["20024192"],"award-info":[{"award-number":["20024192"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies often face limitations in efficacy and safety, necessitating the development of microbiome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes (C. acnes)-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. acnes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including Tumor Necrosis Factor-alpha (TNF-\u03b1), Interleukin (IL)-1\u03b2, and Cyclooxygenase-2 (COX2), whereas IAA demonstrated limited efficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reducing inflammatory cell infiltration, epidermal hyperplasia, and IL-1\u03b2 expression. Transcriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as Cytochrome (CYP) 1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical formulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management.<\/jats:p>","DOI":"10.3390\/ijms27031131","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbiome-Derived Indole-3-Lactic Acid Attenuates Cutibacterium Acnes-Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6237-9031","authenticated-orcid":false,"given":"Sang Gyu","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5384-2603","authenticated-orcid":false,"given":"Nam Hao","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 17000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5569-9579","authenticated-orcid":false,"given":"Seoyoon","family":"Ham","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3463-6661","authenticated-orcid":false,"given":"Yujin","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4466-9550","authenticated-orcid":false,"given":"Ngoc Ha","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Department of Dermatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 17000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3375-8705","authenticated-orcid":false,"given":"Seon Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Bioinformatics Collaboration Unit (BiCU), Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6831-7379","authenticated-orcid":false,"given":"Young In","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1001\/jama.2021.17633","article-title":"Management of Acne Vulgaris: A Review","volume":"326","author":"Eichenfield","year":"2021","journal-title":"JAMA"},{"key":"ref_2","first-page":"101578","article-title":"Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances","volume":"36","author":"Vasam","year":"2023","journal-title":"Biochem. 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