Prevotella copri facilitates wound healing in mice through the sphingosine-CerS1-ceramide metabolic pathway

Sep 29, 2026

Uploaded by Aran

Skin wound repair relies on spatiotemporally coordinated molecular signaling, with growing recognition that skin microbiota actively regulate healing. Using a broad-spectrum antibiotic-treated murine model, Prevotella copri was identified as a key functional commensal that promotes tissue regeneration via metabolite-host crosstalk. ABX-driven microbial remodeling increased P. copri abundance, hastened wound closure, and elevated pro-regenerative factors VEGF and EGF. Metabolomics showed P. copri converts sphingosine to C18-ceramide via the non-canonical CerS1 pathway, stimulating keratinocyte hyperproliferation and neoangiogenesis; CerS1 inhibition suppressed ceramide synthesis and delayed healing, validating the axis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Importance

Keywords

Skin microbiota and wound healing biology

Stages of wound healing

Microbial roles in regeneration

| Host-Microbial Interactions | Research Article Prevotella copri facilitates wound healing in mice through thesphingosine-CerS1-ceramide metabolic pathway Meili Zhao,1 Yue Liu,1 Shuyao Lv,1 Taotao Mi,1 Nan Wang,1 Shuaishuai Zhang,1 Hailiang Liu1,2,3 AUTHOR AFFILIATIONS See affiliation list on p. 16. ABSTRACT Skin wound repair constitutes a sophisticated biological process involving spatiotemporally coordinated molecular cascades, with emerging evidence highlighting the dynamic regulatory role of skin microbiota. Utilizing a broad-spectrum antibiotic (ABX)-treated murine model, we identified Prevotella copri as a core functional commensal in the wound microecosystem that orchestrates tissue regeneration through metabolite-host crosstalk. ABX-induced microbial remodeling significantly enriched P. copri relative abundance, accelerated wound closure, and upregulated pro-regenerative factors vascular endothelial growth factor and epidermal growth factor. Metabolomic profiling revealed that P. copri-secreted sphingosine undergoes bioconversion to C18-ceramide via the non-canonical CerS1 pathway, driving keratinocyte hyperproliferation and neoangiogenesis. Pharmacological inhibition of CerS1 with P053 suppressed ceramide synthesis and delayed healing, mechanistically validating the sphingosineCerS1-ceramide axis. Crucially, P. copri exhibits dual regulatory modalities: ecologically,β-lactamase-mediated antibiotic resistance establishes microbial dominance, while metabolically, sphingolipid-driven spatiotemporal signaling remodels the regenerative microenvironment. These findings align with and extend the evolving perspective of a functional wound microbiota and propose a potential synergistic strategy that combines targeted enrichment of beneficial commensals like P. copri with metabolic axis modulation to promote healing. Our findings elucidate a microecology-metabolism circuit that transitions wound management from passive anti-infection to precision intervention, providing a molecular blueprint for developing microbiome-reprogramming therapies in regenerative medicine. IMPORTANCE Traditional wound repair research often focuses on microbial diversity, neglecting the critical role of specific taxa in tissue regeneration. Our study challenges this by highlighting Prevotella copri as a key species in wound healing, operating through the Prevotella copri-sphingosine-CerS1-ceramide signaling pathway. This discovery reshapes the understanding of microbiome-host interactions and paves the way for precision microbial therapies. By showing that a single bacterium can replace complex community dynamics, we connect ecological theory with regenerative applications, offering a strategy to use microbial metabolism for precise wound healing. KEYWORDS Prevotella copri, Wound healing, Sphingosine, Microbiome-host interactions T he skin, the largest organ of the human body, serves as a critical barrier against the invasion of external pathogens. Diverse microorganisms—including bacteria, fungi, and viruses—colonize the skin surface, forming a complex and dynamic microbiota. Notably, skin microbes, particularly those inhabiting wounds, rarely exist in a free-living planktonic state but instead assemble into structured biofilm communities (1–3) . These biofilms confer enhanced resistance to environmental stressors and antimicrobial agents Editor Yuan Pin Hung, Tainan Hospital Ministry of Health and Welfare, Tainan, Taiwan Address correspondence to Hailiang Liu, hailiang_ 1 [111@tongji.edu.cn](111@tongji.edu.cn). authors declare conflict of interest (4, 5), fundamentally shaping the ecological dynamics and functional impact of the skin microbiota. Prevotella copri, an obligate anaerobe, persists on oxygen-exposed skin by occupying hypoxic niches such as deep hair follicles (>200 µm depth), where restricted oxygen diffusion creates localized anaerobic environments (6) . Its survival is further facilitated through integration i

FAQs

What role does Prevotella copri play in wound healing?

Prevotella copri is identified as a core functional commensal in the wound microecosystem that orchestrates tissue regeneration through metabolite-host crosstalk, leading to faster wound closure and increased pro-regenerative factors.

How does P. copri contribute mechanistically to healing?

P. copri secretes sphingosine that is bioconverted to C18-ceramide via a non-canonical CerS1 pathway, which drives keratinocyte hyperproliferation and neoangiogenesis.

What evidence supports the sphingosine-CerS1-ceramide signaling axis?

Pharmacological inhibition of CerS1 with P053 suppressed ceramide synthesis and delayed healing, directly validating the sphingosine-CerS1-ceramide axis as a causal mechanism.

Sep 29, 2026

Uploaded by Aran