Commensal Cutibacterium acnes-derived indolelactic acid safeguards skin barrier function through the aryl hydrocarbon receptor

  • Cell Rep Med. 2026 Jun 23:102882. doi: 10.1016/j.xcrm.2026.102882.
Shan Zhang  1 ,  Fang Li  2 ,  Xiaoqiang Xu  3 ,  Tianze Yu  3 ,  Yang Liu  4 ,  Xiaokai Fang  5 ,  Yuan Zhou  2 ,  Beilei Xu  2 ,  Yu Zhang  2 ,  Yang Luo  2 ,  Qianjin Lu  2 ,  Xiaochun Liu  6 ,  Wei Li  7 ,  Xu Yao  8
Affiliations
  • 1. Department of Allergy and Rheumatology, Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China; Department of Dermatology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China.
  • 2. Department of Allergy and Rheumatology, Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China.
  • 3. Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
  • 4. 01life Institute, Shenzhen 518000, China.
  • 5. Department of Allergy and Rheumatology, Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China; Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
  • 6. Department of Allergy and Rheumatology, Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China. Electronic address: [email protected].
  • 7. Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: [email protected].
  • 8. Department of Allergy and Rheumatology, Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China. Electronic address: [email protected].
PMID: 42335903 DOI: 10.1016/j.xcrm.2026.102882
Abstract

Skin microbial dysbiosis is a key characteristic of atopic dermatitis (AD). Although Cutibacterium acnes (C. acnes) is the most abundant bacterium in the skin microbiota, its precise functions in AD remain unclear. Here, whole-genome Sequencing of C. acnes isolates reveals strain-level genomic and functional heterogeneity between AD patients and healthy individuals. Metabolomic profiling identifies reduced indolelactic acid (ILA), a tryptophan metabolite, in AD skin and in cultures of AD-associated C. acnes strains. In murine models of epidermal-barrier-damaged and AD-like dermatitis, topical ILA application activates the Aryl Hydrocarbon Receptor (AhR) pathway in keratinocytes, upregulating tight junction proteins and suppressing interleukin (IL)-33 to restore barrier integrity and mitigate dermatitis. A proof-of-concept clinical trial confirms ILA's efficacy in reducing transepidermal water loss and alleviating AD symptoms. Our study establishes C. acnes-derived ILA as a crucial regulator of skin barrier repair via AhR signaling, offering therapeutic potential for AD. Clinical trial registration: ChiCTR2400090988.

Keywords
Cutibacterium acnes; IL-33; atopic dermatitis; indolelactic acid; tight junctions.
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