Redefining The Skin Barrier: A Microbiome-Integrated Multilayered Defense Model

July 2025 in “ Barrier Immunity ”

Jingjing Xia, Mathias Hochgerner, Qingzhen Wei, Xiaoxia Zhong, Jiucun Wang

skin barrier microbiome immune cells Langerhans cells T-cells antimicrobial peptides microbiota-derived metabolites commensal organisms

Studysummary This review synthesizes existing research on the multilayered defense system of the skin, highlighting how physical, chemical, immune, and microbial barriers work together to maintain skin health, with disruptions in one often leading to broader barrier dysfunctions.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

This review redefines the skin barrier as a dynamic ecosystem composed of interconnected physical, chemical, immune, and microbial components. It emphasizes the crucial role of the skin microbiome in maintaining barrier function through niche competition, immune modulation, and reinforcement of physical and chemical defenses. Key findings include the production of antimicrobial peptides and organic acids by skin microbiota, which protect against pathogens and maintain an acidic environment. The review highlights the potential of microbiome-targeting therapies, such as live biotherapeutics and bacteriocin-based antimicrobials, and stresses the importance of precision formulation due to strain-specific effects. Understanding these interactions is vital for managing skin disorders and restoring barrier integrity, suggesting that the skin functions as an integrated superorganism.

View this study on onlinelibrary.wiley.com →

Discuss this study in the Community →

Research cited in this study

10 / 10 results

research JAK-STAT1 as Therapeutic Target for EGFR Deficiency-Associated Inflammation and Scarring Alopecia

8 citations , November 2024 in “EMBO Molecular Medicine”

In this study, researchers found that disrupting EGFR signaling in mice led to increased inflammation and hair follicle damage but that inhibiting the JAK-STAT1 pathway could restore hair growth and skin function.

research Commensal Microbe Regulation of Skin Cells in Disease

19 citations , August 2024 in “Cell Host & Microbe”

research Hair Follicles Modulate Skin Barrier Function

9 citations , June 2024 in “Cell Reports”

This study found that hair follicles play a significant role in regulating skin barrier function, with disruptions in the upper hair follicle affecting the epidermis, influencing processes like desquamation and sebum release, and leading to cell movement into the epidermis.

research Spatial Distribution and Functional Impact of Human Scalp Hair Follicle Microbiota

19 citations , December 2023 in “Journal of Investigative Dermatology”

In this study, researchers found that the human hair follicle microbiota vary by anatomical compartment and donor age, with specific microbes like S. epidermidis potentially influencing hair follicle functions, which suggests new avenues for therapeutic targeting.

research Commensal Microbiome Promotes Hair Follicle Regeneration by Inducing Keratinocyte HIF-1α Signaling and Glutamine Metabolism

1 citations , January 2023 in “Science Advances”

This study found that bacterially induced metabolic changes in stem cells can enhance skin and hair follicle regeneration in both mice and humans, suggesting potential strategies for improving recovery after injury.

research T Cell and Bacterial Microbiota Interaction at Intestinal and Skin Epithelial Interfaces

January 2023 in “Discovery immunology”

T cells and bacteria in the gut and skin help maintain health and protect against disease.

research Skin Microbiome, Metabolome and Skin Phenome, from the Perspectives of Skin as an Ecosystem

5 citations , October 2022 in “Phenomics”

This review explores skin microbiome composition and its ecological interactions, highlighting the role of host and environmental factors in shaping the microbial community, but provides no new research findings.

research Hair Eruption Initiates and Commensal Skin Microbiota Aggravate Adverse Events of Anti-EGFR Therapy

41 citations , December 2019 in “Science Translational Medicine”

This study found that EGFR-targeted cancer therapy can cause skin toxicities by disrupting epidermal signaling, allowing microbiota invasion and inflammation, but identified a potential treatment approach using FGF7 or SOS expression to restore barrier integrity.

Short-Chain Fatty Acids from Cutibacterium Acnes Activate Both a Canonical and Epigenetic Inflammatory Response in Human Sebocytes

research Short-Chain Fatty Acids from Cutibacterium Acnes Activate Both a Canonical and Epigenetic Inflammatory Response in Human Sebocytes

70 citations , February 2019 in “The journal of immunology/The Journal of immunology”

This study found that short-chain fatty acids produced by the skin microbe Propionibacterium acnes may drive inflammatory gene expression in sebocytes, potentially contributing to acne.

research Stress-Induced Production of Chemokines by Hair Follicles Regulates the Trafficking of Dendritic Cells in Skin

286 citations , June 2012 in “Nature Immunology”

In this study, researchers found that mouse hair follicles recruit Langerhans cells by secreting chemokines, acting as key portals for these cells in both mice and humans.