Skin commensal Cutibacterium acnes alleviates UVB-induced solar dermatitis via ceramide-mediated TLR4-MyD88-NF-κB PMID: 41794153

ADC Targets in Oncology

2026-04-10

Skin commensal Cutibacterium acnes alleviates UVB-induced solar dermatitis via ceramide-mediated TLR4-MyD88-NF-κB

Free Radic Biol Med. 2026 Jun:249:76-88. doi: 10.1016/j.freeradbiomed.2026.02.074.

Yaolei Ma ¹ , Zhexin Ni ² , Long Zhu ³ , Ju Yang ⁴ , Yunan Zhang ⁵ , Wenping Liu ⁶ , Rui Wang ⁷ , Yuanbo Sun ⁸ , Jinfeng Liu ⁹ , Pengfei Zhang ¹⁰ , Lingxiang Yu ¹¹ , Chaoji Huangfu ¹² , Yue Gao ¹³ , Wei Zhou ¹⁴

Affiliations

1. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, 301617, China; Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
2. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
3. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China; Department of Traditional Chinese Medicine, Qinghai University, No. 251 Ningda Road, Xining, 810016, China. Electronic address: [email protected].
4. Department of Dermatology, The General Hospital of Western Theater Command PLA, No. 270, Rongdu Avenue, Chengdu, Sichuan, 610083, China. Electronic address: [email protected].
5. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China. Electronic address: [email protected].
6. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, 301617, China; Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
7. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, 301617, China; Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
8. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China; Department of Automation, Tsinghua University, Beijing, 100084, China. Electronic address: [email protected].
9. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, 301617, China; Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
10. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
11. Senior Department of Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China. Electronic address: [email protected].
12. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
13. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].
14. Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, 100850, China. Electronic address: [email protected].

Abstract

Background: The high-altitude environment is characterized by hypobaric hypoxia and intense ultraviolet B (UVB) radiation, contributing to increased incidence of UVB-induced skin injuries, including plateau solar dermatitis (PSD). The role of commensal skin microbiota in mediating photoprotection under such extreme conditions remains poorly understood. This study aimed to identify UVB-protective skin microbiota in high-altitude populations and to elucidate their potential mechanisms in mitigating UVB-induced skin damage.

Methods: Skin microbiota profiles were analyzed by 16S rRNA gene Sequencing in healthy plateau residents and PSD patients. Protective effects were evaluated using a murine model of UVB-induced skin injury and an in vitro UVB-exposed HaCaT keratinocyte model. Integrated transcriptomic, proteomic, and metabolomic analyses were performed to identify candidate bioactive microbial metabolites, followed by functional validation.

Results: Cutibacterium acnes (C. acnes) was significantly enriched in healthy plateau residents compared with PSD patients. Topical application of C. acnes alleviated UVB-induced skin inflammation, Collagen degradation, and DNA damage in mice. Multi-omics analyses revealed dysregulation of sphingolipid metabolism following UVB exposure and highlighted bacterial-derived ceramides as candidate protective metabolites. Two representative ceramides, CER2 and CER14, significantly reduced UVB-induced Apoptosis, oxidative stress, and DNA damage in keratinocytes. These effects were associated with suppression of TLR4-MyD88-NF-κB signaling activity.

Conclusion: This study identifies C. acnes as a commensal bacterium with photoprotective potential against UVB-induced skin damage in high-altitude environments. Ceramide-related lipid metabolites derived from C. acnes contribute to attenuation of UVB-triggered inflammatory signaling and cellular injury, providing new insights into microbiome-based strategies for photoprotection.

Keywords

Ceramide; Cutibacterium acnes; NF-κB signaling; Plateau; UVB-skin injury.