2. Academic Validation
  3. Rothia mucilaginosa membrane vesicles stabilize labile iron to alleviate UVB-induced ferroptosis

Rothia mucilaginosa membrane vesicles stabilize labile iron to alleviate UVB-induced ferroptosis

  • Cell Host Microbe. 2026 Jan 14;34(1):35-51.e9. doi: 10.1016/j.chom.2025.12.008.
Siyuan Fan 1,  Xinyue Cai 2,  Weiqi Wang 3,  Meiling Wu 2,  Xiaoyao Huang 2,  Feng Ding 4,  Hao Guo 2,  Geng Dou 4,  Haotian Luo 4,  Shuai Shao 5,  Jing Guo 2,  Zhenlai Zhu 6,  Peisheng Liu 7,  Linfeng Cheng 8,  Siying Liu 3,  Zihan Li 9,  Kun Xuan 10,  Shiyu Liu 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 4 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 5 Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
  • 6 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral Medicine, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 7 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 8 Department of Medical Microbiology and Parasitology, The Fourth Military Medical University, Xi'an 710032, China.
  • 9 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
  • 10 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
  • 11 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
PMID: 41500222 DOI: 10.1016/j.chom.2025.12.008
Abstract

Ultraviolet irradiation, particularly ultraviolet B (UVB), damages keratinocytes, potentially causing actinic cheilitis. Commensal bacteria help maintain barrier function and protect the host. However, it is unclear if commensal bacteria can protect the host from UVB irradiation. Here, we demonstrate that Rothia mucilaginosa (R. mucilaginosa)-derived membrane vesicles (RMVs) contain ferrochelatase, which stabilizes labile iron in host cells to alleviate UVB-induced Ferroptosis. We demonstrate that R. mucilaginosa abundance on lip vermilion inversely correlates with actinic cheilitis severity in patients. Mechanistically, we find that UVB induces R. mucilaginosa to release RMVs, which are internalized by host cell lysosomes. The ferrochelatase contained within these RMVs catalyzes conversion of Fe2+ and porphyrin into heme, thereby alleviating UVB-induced iron overload and Ferroptosis. Topical application of RMVs relieves actinic cheilitis in patients (ChiCTR, no. ChiCTR2500100015). Collectively, we reveal an iron stabilization mechanism through which commensal bacteria protect the host against UVB and expand our understanding of the relationship between commensal bacteria and hosts.

Keywords

Rothia mucilaginosa; actinic cheilitis; ferroptosis; iron metabolism; membrane vesicles; ultraviolet.

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