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From babyhood to adulthood, the bacteria and fungi on your skin help train your immune system—but when that balance tips, chronic inflammation can follow. This new review reveals how and why. Study: Conversation between skin microbiota and the host: from early life to adulthood .
Image Credit: Corona Borealis Studio / Shutterstock In a recent review published in the journal Experimental & Molecular Medicine , researchers in South Korea investigated the interactions between commensal skin microbiota and the epithelial and immune systems throughout the human lifespan, examining their influence on health and disease. Background Ever wondered why your skin heals differently at different ages or why some people are more prone to conditions like eczema or acne? A clue lies in your skin’s microscopic inhabitants. Human skin is home to billions of microorganisms, including bacteria, fungi, and viruses, that are not just passive passengers.
These commensal microbes actively shape immune responses and tissue repair. From infancy to adulthood, they train immune cells, protect against pathogens, and maintain the integrity of the barrier function. However, imbalances in this ecosystem can drive inflammation and chronic skin diseases.
Despite this knowledge, the molecular pathways and long-term consequences of these microbial interactions remain underexplored, necessitating further research. Skin: A habitat and immune interface Newborns with higher Staphylococcus hominis levels at 2 months old show a 40% lower risk of atopic dermatitis by age 1, suggesting early colonization matters. The skin is more than a protective shield—it is an ecosystem.
Composed of the epidermis, dermis, and subcutaneous tissue, its surface provides niches for a variety of commensal microbiota. These microorganisms, including Staphylococcus epidermidis ( S. epidermidis ), Cutibacterium acnes ( C.
acnes ), experimentally studied Lactobacillus rhamnosus GG, and Malassezia fungi, interact with skin cells, contributing to barrier integrity, hydration, and immune modulation. Commensals like S. epidermidis support wound healing, whereas S.
hominis inhibits the growth of pathogens, such as Staphylococcus aureus ( S. aureus ). Others, like C.
acnes , produce propionic acid (a short-chain fatty acid) that strengthens the skin barrier by activating Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) in keratinocytes. Meanwhile, microbial metabolites, such as indole-3-aldehyde and quinolinic acid, activate the Aryl Hydrocarbon Receptor (AhR) pathway in keratinocytes, reducing inflammation and potentially alleviating diseases like psoriasis. In addition, Malassezia has been shown to inhibit S.
aureus biofilm formation, supporting microbial balance on the skin surface. Skin microbiota regulate both skin homeostasis and barrier function. They enhance barrier function by activating the AhR pathway in keratinocytes.
In addition, metabolites (IAld and quinolinic acid) from skin microbiota relieve skin inflammation by activating AHR signaling in keratinocytes. This pathway inhibits TSLP and the NLRP3 inflammasome, thereby attenuating atopic dermatitis and psoriasis. Commensal microbiota colonization of skin wounds shape CXCL10–bacterial DNA complexes, which activate plasmacytoid dendritic cells (pDCs) to produce type I interferons.
These pDCs promote tissue repair through macrophage-mediated processes. Commensal skin microbiota stimulate keratinocytes to produce stem cell factors (SCFs), which induce mast cell maturation. S.
epidermidis strengthens the skin barrier, promotes tissue repair, maintains homeostasis and induces tolerance to commensal microorganisms. This is achieved by producing ceramides and inducing commensal-specific T cells through interactions with DCs and T reg cells via peptide ligand and antigen recognition. In addition, S.
epidermidis can exacerbate skin inflammation through the expansion of γδ T cells. C. acnes also supports skin barrier function by producing triglycerides and can similarly contribute to inflammation via γδ T cell expansion.
Malassezia, a skin fungus, inhibits biofilm formation of S. aureus. Early life imprinting and immune programming First encounters with skin microbiota during infancy leave lasting marks.
For instance, exposure to riboflavin-producing bacteria, such as S. epidermidis , promotes the development of Mucosal-Associated Invariant T (MAIT) cells and Regulatory T (Treg) cells, which are essential for immune tolerance. These effects persist into adulthood, shaping how the immune system reacts to microbes and injuries.
Studies in mice have shown that early exposure to S. aureus may even protect against the development of atopic dermatitis later in life. Conversely, early antibiotic exposure or disruption of the skin barrier during infancy can lead to increased inflammation and diseases such as psoriasis in adulthood.
These early microbial encounters may lead to immune imprinting through chromatin remodeling and gene accessibility changes, although the permanence of these effects requires further investigation. Microbiota–Immune cell interplay Indole-3-aldehyde, a metabolite from skin bacteria like Lactobacillus, quiets inflammation by steering immune cells toward tolerance instead of attack. Commensal microbes engage in constant crosstalk with skin-resident immune cells like macrophages, Dendritic Cells (DCs), gamma-delta (γδ) T cells, and Innate Lymphoid Cells (ILCs).
For example, S. epidermidis peptides activate DCs, which then prime specific T cells for microbial tolerance. Similarly, skin macrophages regulate bacterial infections by controlling hyaluronic acid breakdown, while DCs and keratinocytes recognize microbes via Toll-Like Receptors (TLRs), triggering immune responses.
When this balance is disturbed, inflammation ensues. S. aureus α-toxin, for instance, activates Protease-Activated Receptor 1 (PAR1) in neurons, causing itching and damage.
In some cases, the same microbes that promote healing can trigger disease if they overgrow or invade deeper skin layers. Skin disorders and microbial shifts Butyrate from S. epidermidis ramps up antimicrobial peptide production in keratinocytes, acting like a natural antibiotic factory on your skin.
Conditions like atopic dermatitis, psoriasis, and acne are tightly linked to microbial imbalance, known as dysbiosis. In atopic dermatitis, reduced filaggrin (a protein crucial for barrier function) leads to overgrowth of S. aureus , which worsens inflammation by stimulating T-helper 2 (Th2) cells through cytokines like Interleukin-33 (IL-33) and Thymic Stromal Lymphopoietin (TSLP).
Psoriasis, affecting 1–3% of the global population, is driven by the Interleukin-23–Interleukin-17 (IL-23–IL-17) axis. Mice lacking microbiota exhibit milder symptoms, indicating that certain bacteria exacerbate inflammation. Staphylococcus warneri and Candida albicans worsen lesions, while Staphylococcus cohnii appears protective, likely by suppressing IL-17 signaling, a key driver of psoriasis inflammation.
Acne, often blamed on C. acnes , is more nuanced. While this bacterium is not necessarily more abundant in acne patients, its balance with other microbes like S.
epidermidis affects inflammation. Acne severity correlates with reduced microbial diversity and increased abundance of Firmicutes and Enterococcus species. The review does not address fungal involvement in acne, and such associations remain unconfirmed.
Friend or foe? The commensal dilemma What determines whether a microbe helps or harms? In healthy conditions, commensals are tolerated. However, under immune suppression or skin barrier defects, even friendly microbes can become opportunistic pathogens. For example, S.
epidermidis may shift from symbiont to threat by producing lipases and proteases. Similarly, Malassezia and C. albicans , typically harmless fungi, can cause disease when immunity falters.
The immune system differentiates friend from foe through various cues, including microbial metabolites and virulence factors. For instance, S. aureus α-toxin limits Treg formation, leading to immune activation instead of tolerance.
While pattern recognition receptors like TLRs are involved in microbial sensing, the review does not detail specific early-life discrimination mechanisms. Understanding this microbial switch could lead to better treatments for inflammatory conditions. Why epigenetics matters Skin microbes like S.
epidermidis may influence immune development by altering chromatin structure and increasing accessibility in key immune genes. Some bacteria produce SCFAs like butyrate, which block histone deacetylases and reduce pathogen growth. Researchers are still investigating how long-lasting these changes are and whether they shape immune memory.
These insights open new doors. Could early-life interventions with probiotics prevent chronic skin diseases? Could microbiota-derived metabolites become next-generation therapies? Exploring the skin microbiome ’s epigenetic influence may help answer these questions. Conclusions To summarize, this study reveals how commensal skin microbiota shape immune development, barrier integrity, and disease susceptibility from early life to adulthood.
These microbes are not passive passengers; they train immune cells, promote tissue repair, and even regulate gene expression through epigenetic modifications. However, disturbances due to genetic mutations, environmental factors, or antimicrobial treatments can trigger inflammatory diseases like atopic dermatitis, psoriasis, and acne. Recognizing the bidirectional crosstalk between skin microbes and host systems emphasizes the need for personalized microbiome-targeted therapies.
Clarifying the long-term effects of microbial interactions on gene expression and immune memory could inform future approaches to managing chronic skin conditions. Harnessing this microbial influence offers promising paths toward better management of chronic skin conditions and overall skin health. Cha, J.
, Kim, T.G. & Ryu, J.
H. Conversation between skin microbiota and the host: from early life to adulthood . Exp Mol Med (2025), DOI: 10.
1038/s12276-025-01427-y, https://www.nature.com/articles/s12276-025-01427-y.
