The Skin as a Natural Antibiotic Centre Against Pathogens - the role of antimicrobial defense

Antimicrobial defense of the skin and its skin microbes.

Skin cells and microbiome, and their antimicrobial defense against pathogens

The Skin can be described as a natural Antibiotic Centre against all kind of pathogens and therefore play a huge role in antimicrobial defense. Our skin is far more than a physical barrier: it functions as an active immune organ hosting a rich and diverse skin microbiome that works together with us to protect against external pathogens by using a comprehensive antimicrobial defense system. Antimicrobial peptides (AMPs) are key components of this defense system. These small peptides, produced both by microbes and host cells, act like natural antibiotics by inhibiting or killing other microbes and helping maintain microbial balance on the skin. Research shows that both bacteria and human cells contribute to this innate defence system, which is crucial for skin health. PubMed+1

Skin microbes and bacterial interactions via AMPs

Within the skin microbiome, commensal bacteria such as Staphylococcus epidermidis coexist with potential opportunistic species like Staphylococcus aureus. Each produces antimicrobial substances that help prevent overgrowth by competitors, supporting microbial homeostasis. When this balance is disrupted — for example by changes in skin pH or inflammation — the reduction of beneficial microbes may allow overgrowth of others, a phenomenon observed in conditions such as atopic dermatitis and other inflammatory skin disorders. Goyen PubMed

'Home made' skin antibiotica

What many may not realize is that it is not only microbes that produce antimicrobial molecules. Human skin cells themselves — particularly keratinocytes — produce host AMPs such as defensins and cathelicidin (LL-37), which have broad antimicrobial activity and are important in innate immune defence. Additionally, skin lipids and sebum contain antimicrobial fatty acids that contribute to inhibiting pathogens at the skin surface. DermNet®+1 Goyen

Comparison of Antimicrobial Substances: Gut Bacteria vs. Skin Bacteria vs. Skin Cells and Sebum

The gut and skin both use antimicrobial molecules to protect their surfaces, but the types, roles and contexts differ:

• Gut bacteria predominantly produce bacterial antimicrobials such as bacteriocins and microcins, which help maintain microbial balance and prevent pathogen colonization in the intestinal environment.

• Skin microbes also produce peptide-based antimicrobial factors, including lantibiotics and other bacteriocin-like AMPs that inhibit pathogens and modulate local immune responses.

• Human skin cells (e.g., keratinocytes) produce host-derived AMPs such as defensins and cathelicidin (LL-37), as well as other antimicrobial molecules that can directly inactivate microbes and signal to the immune system.

• Sebum and skin lipids adds another layer by providing antimicrobial free fatty acids that discourage pathogen survival at the skin surface.

Together these systems create a layered antimicrobial defence that is essential for both skin health and prevention of infection, highlighting the integrated nature of innate immunity across different body environments. PMC

This demonstrates how uniquely the skin and its inhabitants work together to keep our bodies as healthy as possible. It also emphasizes the importance of our behavior (skin care), diet, and lifestyle, which positively but also negatively influences the skin-gut axis in maintaining the health of our skin and skin microbiome. Goyen

Marcelline Goyen BSc skin therapy & author - the Netherlands

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