The skin microbiome plays an important role in health and disease. Researchers have now shown that certain skin bacteria can specifically protect us from the sun’s ultraviolet (UV) radiation by metabolizing cis-urocanic acid with the help of an enzyme called urocanase. This allows the skin to fine-tune its response to UV radiation. The results of the study, published in Elsevier’s Journal of Investigative Dermatology, provide an impressive case study demonstrating the ability of the skin microbiome to reshape the immune functions of the host organism.
Fascinating Interaction Between Sunscreens, Cis-Urocanic Acid and the Skin Microbiome
The skin is home to a huge ecosystem of millions of microorganisms, including bacteria, fungi and viruses. The composition of the skin microbiome is unique, complex and varies greatly depending on anatomical location. Commensal microbes, also known as normal microbiota or indigenous microbiota, live in a beneficial or neutral relationship without causing harm. They adapt their metabolism to the resources available in their microenvironment, feed on the nutrients of our skin and produce different molecules that influence their environment and interact with our skin cells.
Lead researcher VijayKumar Patra, PhD, Centre International de Recherche en Infectiologie, Lyon, France, and Research Department of Photodermatology, Medical University of Graz, Austria, explains: “To date, many internal and external factors have been identified that influence the composition of the skin microbiome. These include various individual parameters such as race, gender, age, hormone levels, diet and hygiene, but environmental factors and the effects of occupation, pollution and climate also play an important role. We have long known that UV radiation modulates immune responses against environmental antigens on the skin surface, and more recently that the skin microbiome plays a role in regulating these responses. What intrigued us was the idea that certain microbes could be actively involved in or even influence UV effects. The overlap between microbial metabolism and host immunity became the focus of our investigation.”
The researchers used a combination of microbiome sequencing, immunological assays, in vitro cultures and gnotobiotic mouse models, in which all microorganisms present are defined, to investigate how skin bacteria respond to UVB radiation, which typically causes sunburn. They discovered that certain skin bacteria specifically metabolize cis-urocanic acid, a photoproduct of an important UV-absorbing chromophore of the stratum corneum, trans-urocanic acid, using an enzyme called urocanase. Compared to trans-urocanic acid, cis-urocanic acid has strong immunomodulatory properties. This microbial metabolism then limits the ability of cis-urocanic acid to inhibit immune responses, meaning that skin bacteria fine-tune our skin’s response to UV radiation. The researchers point to the fascinating interaction between sunscreens, cis-urocanic acid and the microbiome, which compete with each other in and on the stratum corneum, the most superficial layer of skin.
Promising Approaches for Therapy and Prevention
Co-researcher Marc Vocanson, PhD, Centre International de Recherche en Infectiologie, Lyon, France, notes that this is the first time scientists have demonstrated a direct metabolic link between UV radiation, a host-derived molecule and bacterial behavior that influences immune function. Given the growing interest in microbiome research and personalized medicine, understanding these interactions between microbes and hosts could fundamentally change the way we look at sun protection, immune diseases, skin cancer or even treatments such as phototherapy.
According to co-author Peter Wolf, MD, Research Department of Photodermatology, Medical University of Graz, these findings open up new possibilities for microbiome-oriented sun protection that not only protects the skin from UV radiation, but also takes into account how resident microbes can alter the immune landscape after exposure. In the future, topical treatments that modulate microbial metabolism could be used to minimize, maintain or enhance UV-induced immunosuppression when clinically beneficial, for example in phototherapy. According to renowned expert Anna Di Nardo, MD, PhD, of the University of California, San Diego, and the Dermatology Institute San Gallicano IRCCS, Rome, the newly discovered role of microbial metabolism in modulating UV tolerance is changing our understanding of the skin barrier – not just as a structural protective shield, but as a metabolically active, microbially regulated interface. With increasing concerns about UV exposure, skin aging and cancer, a deeper understanding of this axis offers promising approaches for therapy and prevention.